U.S. patent application number 14/267771 was filed with the patent office on 2014-09-11 for ex vivo modifiable multiple medicament final dosage form.
This patent application is currently assigned to SEARETE LLC. The applicant listed for this patent is SEARETE LLC. Invention is credited to Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, JR., Victoria Y.H. Wood.
Application Number | 20140257841 14/267771 |
Document ID | / |
Family ID | 46332302 |
Filed Date | 2014-09-11 |
United States Patent
Application |
20140257841 |
Kind Code |
A1 |
Bangera; Mahalaxmi Gita ; et
al. |
September 11, 2014 |
EX VIVO MODIFIABLE MULTIPLE MEDICAMENT FINAL DOSAGE FORM
Abstract
Described embodiments include a final dosage form for
administering a medicament to an animal, an article of manufacture,
and method. A described final dosage form includes a dosage portion
having a medicament and a release element in a first
medicament-release state. The medicament has a first
bioavailability to the animal. The release element is modifiable ex
vivo to a second medicament-release state by an exposure to a
stimulus, wherein the medicament has a second bioavailability to
the animal. The final dosage form includes another dosage portion
having another medicament and another release element in another
first medicament-release state. In the another first
medicament-release state, the another medicament has another first
bioavailability to the animal. The another release element is
modifiable ex vivo to another second medicament-release state by an
exposure to another stimulus, wherein the another medicament has
another second bioavailability to the animal.
Inventors: |
Bangera; Mahalaxmi Gita;
(Renton, WA) ; Boyden; Edward S.; (Chestnut Hill,
MA) ; Hyde; Roderick A.; (Redmond, WA) ;
Ishikawa; Muriel Y.; (Livermore, CA) ; Rivet; Dennis
J.; (Chesapeake, VA) ; Sweeney; Elizabeth A.;
(Seattle, WA) ; Wood, JR.; Lowell L.; (Bellevue,
WA) ; Wood; Victoria Y.H.; (Livermore, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
SEARETE LLC |
Bellevue |
WA |
US |
|
|
Assignee: |
SEARETE LLC
Bellevue
WA
|
Family ID: |
46332302 |
Appl. No.: |
14/267771 |
Filed: |
May 1, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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12387325 |
Apr 29, 2009 |
8753677 |
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14267771 |
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12284015 |
Sep 16, 2008 |
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12387325 |
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12284014 |
Sep 16, 2008 |
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12284015 |
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12284013 |
Sep 16, 2008 |
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12284014 |
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12322877 |
Feb 5, 2009 |
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12284013 |
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12322874 |
Feb 5, 2009 |
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12322877 |
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12322878 |
Feb 5, 2009 |
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12322874 |
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12387312 |
Apr 29, 2009 |
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12322878 |
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12387326 |
Apr 29, 2009 |
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12387312 |
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12387329 |
Apr 29, 2009 |
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12387326 |
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12387324 |
Apr 29, 2009 |
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12387329 |
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12387323 |
Apr 29, 2009 |
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12387324 |
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12387328 |
Apr 29, 2009 |
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12387323 |
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12387311 |
Apr 29, 2009 |
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12387328 |
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Current U.S.
Class: |
705/2 |
Current CPC
Class: |
G16H 20/10 20180101;
A61K 9/51 20130101; A61P 43/00 20180101; A61K 9/06 20130101; A61K
9/127 20130101; A61K 9/4891 20130101 |
Class at
Publication: |
705/2 |
International
Class: |
G06F 19/00 20060101
G06F019/00 |
Claims
1. A final dosage form for administering medicament to an animal,
the final dosage form comprises: a dosage portion having a
medicament; and a release element in a first medicament-release
state wherein the medicament has a first bioavailability to the
animal if the final dosage form is administered to the animal in
the first medicament-release state, the release element modifiable
ex vivo to a second medicament-release state by an exposure to a
stimulus, wherein the medicament has a second bioavailability to
the animal if the final dosage form is administered to the animal
in the second medicament-release state; and another dosage portion
having another medicament; and another release element in another
first medicament-release state wherein the another medicament has
another first bioavailability to the animal if the final dosage
form is administered to the animal in the another first
medicament-release state, the another release element modifiable ex
vivo to another second medicament-release state by an exposure to
another stimulus, wherein the another medicament has another second
bioavailability to the animal if the final dosage form is
administered to the animal in the another second medicament-release
state.
2. The final dosage form of claim 1, wherein the first
medicament-release state wherein the medicament has a first
bioavailability to the animal includes: a first medicament-release
state wherein the medicament is not bioavailable to the animal.
3. The final dosage form of claim 1, wherein the first
medicament-release state wherein the medicament has a first
bioavailability to the animal includes: a first medicament-release
state wherein the medicament is bioavailable to the animal.
4. The final dosage form of claim 1, wherein the second
medicament-release state wherein the medicament has a second
bioavailability to the animal includes: a second medicament-release
state wherein the medicament is not bioavailable to the animal.
5. The final dosage form of claim 1, wherein the second
medicament-release state wherein the medicament has a second
bioavailability to the animal includes: a second medicament-release
state wherein the medicament is bioavailable to the animal.
6. The final dosage form of claim 1, wherein the another first
medicament-release state wherein the another medicament has another
first bioavailability to the animal includes: another first
medicament-release state wherein the another medicament is not
bioavailable to the animal.
7. The final dosage form of claim 1, wherein the another first
medicament-release state wherein the another medicament has another
first bioavailability to the animal includes: another first
medicament-release state wherein the another medicament is
bioavailable to the animal.
8. The final dosage form of claim 1, wherein the another second
medicament-release state wherein the another medicament has another
second bioavailability to the animal includes: another second
medicament-release state wherein the another medicament is not
bioavailable to the animal.
9. The final dosage form of claim 1, wherein the another second
medicament-release state wherein the another medicament has another
second bioavailability to the animal includes: another second
medicament-release state wherein the another medicament is
bioavailable to the animal.
10. The final dosage form of claim 1, wherein the first
bioavailability to the animal includes a first bioavailability
characteristic and the second bioavailability to the animal
includes a second bioavailability characteristic.
11. The final dosage form of claim 1, wherein the stimulus
includes: at least one of a mechanical stimulus, a non-ionizing
radiation stimulus, an ionizing radiation stimulus, a chemical
stimulus, an acoustic stimulus, an ultrasound stimulus, a radio
wave stimulus, a microwave stimulus, a light wave stimulus, or a
thermal stimulus.
12. A final dosage form for administering a medicament to an
animal, the final dosage form comprises: a dosage portion having: a
medicament; a release element in a medicament-holding state wherein
the medicament is substantially not bioavailable to the animal if
the final dosage form is administered to the animal in the
medicament-holding state, the release element modifiable ex vivo to
a medicament-discharging state by an exposure to a stimulus wherein
the medicament is bioavailable to the animal if the final dosage
form is administered to the animal in the medicament-discharging
state; and another dosage portion having another medicament;
another release element in another medicament-holding state wherein
the another medicament is substantially not bioavailable to the
animal if the final dosage form is administered to the animal in
the another medicament-holding state, the another release element
modifiable ex vivo to another medicament-discharge state by an
exposure to another stimulus wherein the another medicament is
bioavailable to the animal if the final dosage form is administered
to the animal in the another medicament-discharge state.
13. The final dosage form of claim 12, further comprising: an outer
layer carrying the dosage portion and the another dosage
portion.
14. A method of modifying medicament bioavailability of a final
dosage form for administering medicament to an animal, wherein the
final dosage form includes a dosage portion having a medicament;
and a release element in a first medicament-release state wherein
the medicament has a first bioavailability to the animal if the
final dosage form is administered to the animal in the first
medicament-release state, the release element modifiable ex vivo to
a second medicament-release state by an exposure to a stimulus,
wherein the medicament has a second bioavailability to the animal
if the final dosage form is administered to the animal in the
second medicament-release state; and another dosage portion having
another medicament; and another release element in another first
medicament-release state wherein the another medicament has another
first bioavailability to the animal if the final dosage form is
administered to the animal in the another first medicament-release
state, the another release element modifiable ex vivo to another
second medicament-release state by an exposure to another stimulus,
wherein the another medicament has another second bioavailability
to the animal if the final dosage form is administered to the
animal in the another second medicament-release state; the method
comprising: transforming the final dosage form into a selected
medicament release profile by initiating an ex vivo exposure of the
release element or the another release element to a modification
stimulus respectfully selected from the stimulus or the another
stimulus.
15. The method of claim 14, further comprising: receiving a signal
indicative of a chosen medicament bioavailability of the final
dosage form.
16. The method of claim 15, wherein receiving signal indicative of
a chosen medicament bioavailability of the final dosage form
includes: receiving a machine-initiated signal indicative
indication of a chosen medicament bioavailability of the final
dosage form.
17. The method of claim 15, wherein receiving signal indicative of
a chosen medicament bioavailability of the final dosage form
includes: receiving a human-initiated signal indicative of a chosen
medicament bioavailability of the final dosage form.
18. The method of claim 14, further comprising: selecting a
medicament-release state of the release element or of the another
release element in response to the chosen
medicament-bioavailability of the final dosage form.
19. The method of claim 18, wherein the selecting a
medicament-release state of the release element or of the another
release element in response to the selected
medicament-bioavailability of the final dosage form includes:
electronically selecting a medicament-release state of the release
element or of the another release element in response to the
selected medicament-bioavailability of the final dosage form, the
selecting a medicament-release state based on an
electronically-stored database relating medicament-release state
and medicament-bioavailability of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-release state and medicament-bioavailability of the
final dosage form.
20. The method of claim 14, further comprising: selecting the
stimulus for initiation from the stimulus or the another stimulus
in response to the selected medicament-release state.
21. The method of claim 20, wherein the selecting the modification
stimulus from the stimulus or the another stimulus in response to
the selected medicament-release state includes: electronically
selecting the modification stimulus from the stimulus or the
another stimulus in response to the selected medicament-release
state, the selecting the stimulus based on an electronically-stored
database relating stimuli and medicament-release state of the final
dosage form, a computer-implemented decision table, a
digitally-maintained final dosage form transformation table, or a
digital library correlating medicament-release state of the final
dosage form and stimuli.
22. The method of claim 14, wherein the transforming the final
dosage form into a selected medicament release profile by
initiating an ex vivo exposure of the release element or the
another release element to a modification stimulus respectfully
selected from the stimulus or the another stimulus includes:
transforming the final dosage form into a selected medicament
release profile by initiating an ex vivo exposure of the release
element and the another release element to the stimulus and the
another stimulus.
23. An article of manufacture comprising: a final dosage form for
administering medicament to an animal, the final dosage form
including a dosage portion having a medicament; and a release
element in a first medicament-release state wherein the medicament
has a first bioavailability to the animal if the final dosage form
is administered to the animal in the first medicament-release
state, the release element modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus, wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal in the second
medicament-release state; and another dosage portion having another
medicament another release element in another first
medicament-release state wherein the another medicament has another
first bioavailability to the animal if the final dosage form is
administered to the animal in the another first medicament-release
state, the another release element modifiable ex vivo to another
second medicament-release state by an exposure to another stimulus,
wherein the another medicament has another second bioavailability
to the animal if the final dosage form is administered to the
animal in the another second medicament-release state; and
instructions specifying an ex vivo exposure of the release element
to the stimulus or an ex vivo exposure of the another release
element to the another stimulus which when implemented respectfully
transform the release element to the second medicament-release
state or the another release element to the another second
medicament-release state.
24. An article of manufacture for administering medicament to an
animal, the article comprising: a medicament; means for medicament
release control in a first state wherein the medicament has a first
bioavailability to the animal if the article of manufacture is
administered to the animal, the means for medicament release
control modifiable ex vivo to a second state by an exposure to a
stimulus, wherein the medicament has a second bioavailability to
the animal if the article of manufacture is administered to the
animal; another medicament; and another means for medicament
release control in another first state wherein the another
medicament has another first bioavailability to the animal if the
article of manufacture is administered to the animal, the another
means for medicament release control modifiable ex vivo to another
second state by an exposure to another stimulus, wherein the
another medicament has another second bioavailability to the animal
if the article of manufacture is administered to the animal.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is related to and claims the benefit
of the earliest available effective filing date(s) from the
following listed application(s) (the "Related Applications") (e.g.,
claims earliest available priority dates for other than provisional
patent applications or claims benefits under 35 USC .sctn.119(e)
for provisional patent applications, for any and all parent,
grandparent, great-grandparent, etc. applications of the Related
Application(s)).
RELATED APPLICATIONS
[0002] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/284,015, titled INDIVIDUALIZABLE
DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden,
Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A.
Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors,
filed Sep. 16, 2008, which is currently co-pending, or is an
application of which a currently co-pending application is entitled
to the benefit of the filing date.
[0003] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/284,014, titled PERSONALIZABLE
DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden,
Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A.
Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors,
filed Sep. 16, 2008, which is currently co-pending, or is an
application of which a currently co-pending application is entitled
to the benefit of the filing date.
[0004] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/284,013, titled MODIFIABLE DOSAGE
FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A.
Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney,
Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed
Sep. 16, 2008, which is currently co-pending, or is an application
of which a currently co-pending application is entitled to the
benefit of the filing date.
[0005] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/322,877, titled EX VIVO-MODIFIABLE
PARTICLE OR POLYMERIC BASED FINAL DOSAGE FORM, naming Mahalaxmi
Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y.
Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood,
Jr., and Victoria Y. H. Wood as inventors, filed Feb. 5, 2009,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0006] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/322,874, titled MODIFYING A
MEDICAMENT AVAILABILITY STATE OF A FINAL DOSAGE FORM, naming
Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel
Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood,
Jr., and Victoria Y. H. Wood as inventors, filed Feb. 5, 2009,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0007] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of U.S.
patent application Ser. No. 12/322,878, titled EX VIVO ACTIVATABLE
DOSAGE FORM, naming Mahalaxmi Gita Bangera, Edward S. Boyden,
Roderick A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A.
Sweeney, Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors,
filed Feb. 5, 2009, which is currently co-pending, or is an
application of which a currently co-pending application is entitled
to the benefit of the filing date.
[0008] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of United
States patent application No. To be assigned, titled EX VIVO
MODIFIABLE PARTICLE OR POLYMERIC MEDICAMENT CARRIER, naming
Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel
Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood,
Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0009] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of United
States patent application No. To be assigned, titled EX
VIVO-MODIFIABLE MULTIPLE-RELEASE STATE FINAL DOSAGE FORM medicament
carrier, naming Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick
A. Hyde, Muriel Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney,
Lowell L. Wood, Jr., and Victoria Y. H. Wood as inventors, filed
Apr. 29, 2009, which is currently co-pending, or is an application
of which a currently co-pending application is entitled to the
benefit of the filing date.
[0010] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of United
States patent application No. To be assigned, titled SYSTEM FOR EX
VIVO MODIFICATION OF MEDICAMENT RELEASE STATE, naming Mahalaxmi
Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y.
Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood,
Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0011] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of United
States patent application No. To be assigned, titled MULTIPLE
CHAMBER EX VIVO ADJUSTABLE-RELEASE FINAL DOSAGE FORM, naming
Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel
Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood,
Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0012] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of United
States patent application No. To be assigned, titled EX VIVO
MODIFIABLE MEDICAMENT RELEASE-SITES FINAL DOSAGE FORM, naming
Mahalaxmi Gita Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel
Y. Ishikawa, Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood,
Jr., and Victoria Y. H. Wood as inventors, filed Apr. 29, 2009,
which is currently co-pending, or is an application of which a
currently co-pending application is entitled to the benefit of the
filing date.
[0013] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of United
States patent application No. To be assigned, titled EX VIVO
MODIFIABLE MEDICAMENT RELEASE-ASSOCIATIONS, naming Mahalaxmi Gita
Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa,
Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and
Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0014] For purposes of the USPTO extra-statutory requirements, the
present application constitutes a continuation-in-part of United
States patent application No. To be assigned, titled EX VIVO
MODIFIABLE MEDICAMENT RELEASE-SUBSTANCE, naming Mahalaxmi Gita
Bangera, Edward S. Boyden, Roderick A. Hyde, Muriel Y. Ishikawa,
Dennis J. Rivet, Elizabeth A. Sweeney, Lowell L. Wood, Jr., and
Victoria Y. H. Wood as inventors, filed Apr. 29, 2009, which is
currently co-pending, or is an application of which a currently
co-pending application is entitled to the benefit of the filing
date.
[0015] The United States Patent Office (USPTO) has published a
notice to the effect that the USPTO's computer programs require
that patent applicants reference both a serial number and indicate
whether an application is a continuation or continuation-in-part.
Stephen G. Kunin, Benefit of Prior-Filed Application, USPTO
Official Gazette Mar. 18, 2003, available at
http://www.uspto.gov/web/offices/com/sol/og/2003/week11/patbene.htm.
The present Applicant Entity (hereinafter "Applicant") has provided
above a specific reference to the application(s) from which
priority is being claimed as recited by statute. Applicant
understands that the statute is unambiguous in its specific
reference language and does not require either a serial number or
any characterization, such as "continuation" or
"continuation-in-part," for claiming priority to U.S. patent
applications. Notwithstanding the foregoing, Applicant understands
that the USPTO's computer programs have certain data entry
requirements, and hence Applicant is designating the present
application as a continuation-in-part of its parent applications as
set forth above, but expressly points out that such designations
are not to be construed in any way as any type of commentary or
admission as to whether or not the present application contains any
new matter in addition to the matter of its parent
application(s).
[0016] All subject matter of the Related Applications and of any
and all parent, grandparent, great-grandparent, etc. applications
of the Related Applications is incorporated herein by reference to
the extent such subject matter is not inconsistent herewith.
SUMMARY
[0017] An embodiment of the subject matter described herein
describes a final dosage form for administering medicament to an
animal. The final dosage form includes a dosage portion having a
medicament and a release element in a first medicament-release
state. In the first medicament-release state, the medicament has a
first bioavailability to the animal if the final dosage form is
administered to the animal in the first medicament-release state.
The release element is modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus, wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal in the second
medicament-release state. The final dosage form includes another
dosage portion having another medicament and another release
element in another first medicament-release state. In the another
first medicament-release state, the another medicament has another
first bioavailability to the animal if the final dosage form is
administered to the animal in the another first medicament-release
state. The another release element is modifiable ex vivo to another
second medicament-release state by an exposure to another stimulus,
wherein the another medicament has another second bioavailability
to the animal if the final dosage form is administered to the
animal in the another second medicament-release state.
[0018] An embodiment of the subject matter described herein
describes a final dosage form for administering medicament to an
animal. The final dosage form includes a dosage portion having a
medicament and a release element in a medicament-holding state. In
the medicament-holding state, the medicament is substantially not
bioavailable to the animal if the final dosage form is administered
to the animal in the medicament-holding state. The release element
is modifiable ex vivo to a medicament-discharging state by an
exposure to a stimulus wherein the medicament is bioavailable to
the animal if the final dosage form is administered to the animal
in the medicament-discharging state. The final dosage form includes
another dosage portion having another medicament and another
release element in another medicament-holding state. In the another
medicament-holding state, the another medicament is substantially
not bioavailable to the animal if the final dosage form is
administered to the animal in the another medicament-holding state.
The another release element is modifiable ex vivo to another
medicament-discharge state by an exposure to another stimulus
wherein the another medicament is bioavailable to the animal if the
final dosage form is administered to the animal in the another
medicament-discharge state. In an embodiment, the final dosage form
may include an outer layer carrying the dosage portion and the
another dosage portion.
[0019] An embodiment of the subject matter described herein
describes a method of modifying medicament bioavailability of a
final dosage form for administering medicament to an animal. The
final dosage form includes a dosage portion having a medicament and
a release element in a first medicament-release state. In the first
medicament-release state, the medicament has a first
bioavailability to the animal if the final dosage form is
administered to the animal in the first medicament-release state.
The release element is modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus, wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal in the second
medicament-release state. The final dosage form includes another
dosage portion having another medicament and another release
element in another first medicament-release state. In another first
medicament-release state, the another medicament has another first
bioavailability to the animal if the final dosage form is
administered to the animal in the another first medicament-release
state. The another release element is modifiable ex vivo to another
second medicament-release state by an exposure to another stimulus,
wherein the another medicament has another second bioavailability
to the animal if the final dosage form is administered to the
animal in the another second medicament-release state. The method
includes transforming the final dosage form into a selected
medicament release profile by initiating an ex vivo exposure of the
release element or the another release element to a modification
stimulus respectfully selected from the stimulus or the another
stimulus. In an embodiment, the method may include receiving a
signal indicative of a chosen medicament bioavailability of the
final dosage form. In an embodiment, the method may include
selecting a medicament-release state of the release element or of
the another release element in response to the chosen
medicament-bioavailability of the final dosage form. In an
embodiment, the method may include selecting the stimulus for
initiation from the stimulus or the another stimulus in response to
the selected medicament-release state.
[0020] An embodiment of the subject matter described herein
describes an article of manufacture. The article of manufacture
includes a final dosage form for administering medicament to an
animal. The final dosage form includes a dosage portion having a
medicament and a release element in a first medicament-release
state. In the first medicament-release state, the medicament has a
first bioavailability to the animal if the final dosage form is
administered to the animal in the first medicament-release state.
The release element is modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus, wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal in the second
medicament-release state. The final dosage form includes another
dosage portion having another medicament and another release
element in another first medicament-release state. In another first
medicament-release state, the another medicament has another first
bioavailability to the animal if the final dosage form is
administered to the animal in the another first medicament-release
state. The another release element is modifiable ex vivo to another
second medicament-release state by an exposure to another stimulus,
wherein the another medicament has another second bioavailability
to the animal if the final dosage form is administered to the
animal in the another second medicament-release state. The article
of manufacture includes instructions specifying an ex vivo exposure
of the release element to the stimulus or an ex vivo exposure of
the another release element to the another stimulus which when
implemented respectfully transform the release element to the
second medicament-release state or the another release element to
the another second medicament-release state.
[0021] An embodiment of the subject matter described herein
describes an article of manufacture for administering medicament to
an animal. The article includes a medicament. The article also
includes means for medicament release control in a first state
wherein the medicament has a first bioavailability to the animal if
the article of manufacture is administered to the animal. The means
for medicament release control is modifiable ex vivo to a second
state by an exposure to a stimulus, wherein the medicament has a
second bioavailability to the animal if the article of manufacture
is administered to the animal. The article includes another
medicament. The article also includes another means for medicament
release control in another first state wherein the another
medicament has another first bioavailability to the animal if the
article of manufacture is administered to the animal. The another
means for medicament release control is modifiable ex vivo to
another second state by an exposure to another stimulus, wherein
the another medicament has another second bioavailability to the
animal if the article of manufacture is administered to the
animal.
[0022] The foregoing summary is illustrative only and is not
intended to be in any way limiting. In addition to the illustrative
aspects, embodiments, and features described above, further
aspects, embodiments, and features will become apparent by
reference to the drawings and the following detailed
description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0023] FIG. 1 illustrates an example environment that includes an
animal, a cross-sectional view of an example final dosage form for
administering a medicament to the animal, and an example
stimulation source operable to emit a stimulus;
[0024] FIG. 2 illustrates another example environment that includes
the animal, a cross-sectional view of an example final dosage form
for administering a medicament to the animal, and the example
stimulation source operable to emit the stimulus;
[0025] FIG. 3 illustrates a further example environment that
includes the animal, a cross-sectional view of an example final
dosage form for administering a medicament to the animal, and the
example stimulation source operable to emit the stimulus;
[0026] FIG. 4 illustrates another example environment that includes
the animal, a cross-sectional view of an example final dosage form
for administering a medicament to the animal, and the example
stimulation source operable to emit the stimulus;
[0027] FIG. 5 illustrates a further example environment that
includes an animal, a cross-sectional view of an example final
dosage form for transporting medicament to the animal;
[0028] FIG. 6 illustrates an example environment that includes an
article of manufacture;
[0029] FIG. 7 illustrates an example operational flow modulating a
medicament-release characteristic of a final dosage form;
[0030] FIG. 8 illustrates an alternative embodiment of the
operational flow of FIG. 7;
[0031] FIG. 9 illustrates an example operational flow fulfilling a
request specifying a dose of a medicament for an individual
animal;
[0032] FIG. 10 illustrates an alternative embodiment of the example
operational flow of FIG. 9;
[0033] FIG. 11 illustrates another alternative embodiment of the
example operational flow of FIG. 9
[0034] FIG. 12 illustrates a further embodiment of the example
operation of FIG. 9;
[0035] FIG. 13 illustrates another embodiment of the example
operational flow of FIG. 9;
[0036] FIG. 14 illustrates a further embodiment of the example
operational flow of FIG. 9.
[0037] FIG. 15 illustrates an example environment that includes an
animal, a cross-sectional view of an example final dosage form for
administering the medicament to the animal, and the example
stimulation source operable to emit a stimulus;
[0038] FIG. 16 illustrates an example environment that illustrates
a final dosage form having a release element implemented by a
characteristic response of a particle or a polymer to the
stimulus;
[0039] FIG. 17 illustrates an example environment that includes an
article;
[0040] FIG. 18 illustrates an example operational flow modifying a
medicament availability characteristic of a final dosage form;
[0041] FIG. 19 illustrates an example final dosage form for
administering a medicament to an animal;
[0042] FIG. 20 illustrates an example environment that includes a
final dosage form 1502 configurable to administer a medicament to
an animal;
[0043] FIG. 21 illustrates an example environment depicting
retention and release states of particle or polymeric material
(depicted as a hydrogel) responsive to an ex vivo stimulus;
[0044] FIG. 22 illustrates an example environment that includes an
article of manufacture;
[0045] FIG. 23 illustrates an example environment that includes a
final dosage form for administering the medicament to an
animal;
[0046] FIG. 24 illustrates an example environment that includes a
final dosage form and an operational flow;
[0047] FIG. 25 illustrates alternative embodiments of the
activation operation of FIG. 24;
[0048] FIG. 26 illustrates an example embodiment of a final dosage
form for administering a medicament;
[0049] FIG. 27 illustrates an example system in which embodiments
may be implemented;
[0050] FIG. 28 illustrates an example environment that includes a
final dosage form for administering the medicament to an
animal;
[0051] FIG. 29 illustrates an example environment that includes a
final dosage form for administering the medicament to an
animal;
[0052] FIG. 30 illustrates an example environment that includes a
final dosage form and an operational flow;
[0053] FIG. 31 illustrates an example article of manufacture for
administering medicament to an animal;
[0054] FIG. 32 illustrates an example environment that includes a
final dosage form for administering medicament to an animal;
[0055] FIG. 33 illustrates an example environment that includes an
article of manufacture;
[0056] FIG. 34 illustrates an example environment that includes a
final dosage form and an operational flow;
[0057] FIG. 35 illustrates an alternative embodiment of the
individualization operation of FIG. 34;
[0058] FIG. 36 illustrates an alternative embodiment of the
individualization operation of FIG. 34;
[0059] FIG. 37 illustrates an alternative embodiment of the
operational flow of FIG. 34;
[0060] FIG. 38 illustrates an example environment that includes a
final dosage form and an operational flow;
[0061] FIG. 39 illustrates an example vehicle for administering a
medicament to an animal;
[0062] FIG. 40 illustrates an example system;
[0063] FIG. 41 illustrates an example environment;
[0064] FIG. 42 illustrates an example environment that includes a
final dosage form for administering medicament to an animal;
[0065] FIG. 43 illustrates an example environment that includes a
final dosage form and an operational flow;
[0066] FIG. 44 illustrates an alternative embodiment of the
operational flow of FIG. 43;
[0067] FIG. 45 illustrates an example environment that includes an
article of manufacture;
[0068] FIG. 46 illustrates an example article of manufacture for
administering medicament to an animal;
[0069] FIG. 47 illustrates an environment that includes a final
dosage form for administering medicament to an animal;
[0070] FIG. 48 illustrates an example environment that includes a
final dosage form for administering medicament to an animal;
[0071] FIG. 49 illustrates an example environment that includes a
final dosage form and an operational flow;
[0072] FIG. 50 illustrates an example alternative embodiment of the
operational flow of FIG. 49;
[0073] FIG. 51 illustrates an example environment that includes an
article of manufacture 4001;
[0074] FIG. 52 illustrates an example environment that includes an
article of manufacture;
[0075] FIG. 53 illustrates an example article of manufacture for
administering medicament to an animal;
[0076] FIG. 54 illustrates an example environment that includes a
final dosage form for administering medicament to an animal;
[0077] FIG. 55 illustrates an example environment that includes a
final dosage form and an operational flow;
[0078] FIG. 56 illustrates an alternative embodiment of the
operational flow described in FIG. 55;
[0079] FIG. 57 illustrates an example environment;
[0080] FIG. 58 illustrates an example article of manufacture for
administering medicament to an animal;
[0081] FIG. 59 illustrates an example environment that includes a
final dosage form for administering medicament to an animal;
[0082] FIG. 60 illustrates an example environment that includes a
final dosage form for administering medicament to an animal and an
operational flow;
[0083] FIG. 61 illustrates an alternative embodiment of the
operational flow described in conjunction with FIG. 60;
[0084] FIG. 62 illustrates an example article of manufacture for
administering medicament to an animal;
[0085] FIG. 63 illustrates an example environment that includes a
final dosage form for administering medicament to an animal;
[0086] FIG. 64 illustrates an example environment that includes a
final dosage form for administering medicament to an animal;
[0087] FIG. 65 illustrates an example environment that includes a
final dosage form and an operational flow;
[0088] FIG. 66 illustrates an alternative embodiment of the
operational flow described in conjunction with FIG. 65; and
[0089] FIG. 67 illustrates an example article of manufacture for
administering medicament to an animal.
DETAILED DESCRIPTION
[0090] In the following detailed description, reference is made to
the accompanying drawings, which form a part hereof. In the
drawings, similar symbols typically identify similar components,
unless context dictates otherwise. The illustrated embodiments
described in the detailed description, drawings, and claims are not
meant to be limiting. Other embodiments may be utilized, and other
changes may be made, without departing from the spirit or scope of
the subject matter presented here.
[0091] FIG. 1 illustrates an environment 100 that includes an
animal 198, a cross-sectional view of an example final dosage form
102 for administering the medicament 190 to an animal, such as the
animal 198, and an example stimulus source 194 configured to emit a
stimulus 192. In an embodiment, the final dosage form includes a
dosage form having completed a manufacturing or production process.
In an embodiment, the final dosage form includes a product,
finished tablet, or capsule ready for distribution to a hospital,
pharmacy, or retail store for individualizing to a particular
animal, such as the animal 198. In an embodiment, the final dosage
form includes a tablet shape, a spherical shape, or an ellipsoidal
shape. In an embodiment, the final dosage form includes a structure
or a particle carryable or transportable by a liquid or other fluid
carrier.
[0092] In an embodiment, the animal 198 includes any living being
capable of voluntary movement and possessing specialized sense
organs. In an embodiment, the animal includes a human. In an
embodiment, the animal includes a mammal. In an embodiment,
administering, administration, or administer the medicament to the
animal includes give or apply the medicament 190 to the animal. In
an embodiment, administering the medicament to the animal includes
dispensing the medicament to the animal. In an embodiment,
administering the medicament to the animal includes delivering the
medicament to the animal. In an embodiment, administering the
medicament to the animal includes directly or indirectly injecting
the medicament to the animal. In an embodiment, administering the
medicament to the animal includes applying the medicament to the
animal. In an embodiment, administering the medicament to the
animal includes providing the medicament to the animal.
[0093] The final dosage form 102 includes an outer layer 110, a
release element 130, and a chamber 120. The release element 130 is
configured in a first medicament-release state and modifiable ex
vivo to a second medicament-release state by an exposure to a
stimulus. For example, the stimulus may include the stimulus 192.
The chamber 120 includes a chamber wall 122, which is substantially
within the outer layer 110, and is configured to carry the
medicament 190. In an embodiment, the final dosage form 102
includes an intermediate outer layer (not shown) with the release
element interposed between the outer layer and the intermediate
outer layer, and the chamber is substantially within the
intermediate outer layer (not shown).
[0094] In an embodiment, the outer layer 110 of the final dosage
form 102 includes an outer layer of at least one of a tablet,
capsule, particle, or solid final dosage form. In an embodiment,
the outer layer 110 includes an outer peripheral layer. FIG. 1
illustrates an example embodiment where the outer layer 110
includes an outer layer around the chamber wall 122 and the release
element 130. In an embodiment, the outer layer 110 is configured
for administration to the animal 198 by at least one of an oral,
enteral, inhalation, or implant route. In an embodiment, an enteral
route includes a rectal route, or a vaginal route, such as by a
suppository. In an embodiment, the outer layer is configured for
administration to the animal by at least one of parenteral, nasal,
auditory canal, pulmonary, topical, or subdermal route.
[0095] In an embodiment, the outer layer 110 includes an outer
layer configured to release the medicament in an in vivo
environment of the animal. In an embodiment, the outer layer 110
includes an outer surface. In an embodiment, the outer layer
includes an outer surface of a biocompatible medicament
administration vehicle or transport.
[0096] In an embodiment, the outer layer 110 of the final dosage
form 102 includes an erodible outer layer. Formulations of erodible
dosage forms are known in the art. In an embodiment, the erodible
outer layer includes an erodible outer layer that is at least one
of soluble, permeable, or disintegrable within the animal 198. In
an embodiment, the erodible outer layer includes an erodible outer
layer having at least a portion that is at least one of soluble,
permeable, or disintegrable in response to an acidic environment
within the animal. In an embodiment, the erodible outer layer
includes an erodible outer layer having at least a portion that is
at least one of soluble, permeable, or disintegrable in response to
a pH neutral or a basic environment within the animal.
[0097] In an embodiment, the outer layer 110 of the final dosage
form 102 includes an outer portion of a plurality of particles.
Examples of such a particle include one or more of hydrogels,
microspheres, polymeric microspheres, and nanoparticles as
described in Lin et al., Hydrogels in controlled release
formulations: Network design and mathematical modeling, ADVANCED
DRUG DELIVERY REVIEWS 58 (2006) (1379-1408). In an embodiment, the
outer layer 110 of the final dosage form 102 includes an outer
portion of an aggregation of molecules. An embodiment includes an
outer layer 110 configured to allow an in vivo discharge of at
least a portion of the medicament 190 from the chamber 120 after an
exposure of the release element 130 to the stimulus 192. An
embodiment includes an outer layer 110 configured in cooperation
with the release element 130 to allow an in vivo discharge of at
least a portion of the medicament 190 from the chamber 120 after an
exposure of the release element 130 to the stimulus. In an
embodiment, the outer layer 110 includes an outer layer of at least
a portion of the release element. In an embodiment, the release
element forms the outer layer. An embodiment includes an outer
layer configured to contain the medicament until the final dosage
form is administered into the animal.
[0098] In an embodiment of the release element 130, the first
medicament-release state is configured to retard medicament release
in vivo and the second medicament-release state is configured to
allow medicament release in vivo. In an embodiment of the release
element 130, the first medicament-release state is configured to
allow medicament release in vivo and the second medicament-release
state is configured to retard medicament release in vivo.
[0099] FIG. 1 illustrates a release element 130 disposed within the
outer layer 110. In an embodiment, the release element includes a
release element that is at least partially disposed within the
outer layer, or a release element that is not disposed within the
outer layer. For example, FIG. 2 infra, illustrates an example of a
final dosage form 202 that includes a release element 230 that is
not disposed within the outer layer 210. FIG. 3, infra, illustrates
an example of a final dosage form 302 that includes a release
element 330 disposed at least partially within the outer layer
310.
[0100] Returning to FIG. 1, in an embodiment, a release element 130
may be configured in a first medicament-release state and
modifiable ex vivo to a second medicament-release state by an
exposure to the stimulus 192. An embodiment includes a release
element configured in a first medicament-release state and
reconfigurable to a second medicament-release state by an exposure
to the stimulus.
[0101] In an embodiment, the release element 130 includes a release
element configured in a first medicament-release state and
modifiable ex vivo to a second medicament-release state by an
exposure to a non-ionizing radiation, illustrated as the stimulus
192. In an embodiment, the release element 130 is configured in a
first medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure to an electromagnetic
radiation, illustrated as the stimulus 192. In an embodiment, the
release element 130 is configured in a first medicament-release
state and modifiable ex vivo to a second medicament-release state
by an exposure to a light radiation, also illustrated as the
stimulus 192. For example, light radiation may include at least one
of the spectrum of ultraviolet (UV), visible light, /or infrared
(IR).
[0102] In an embodiment, the release element 130 includes, but is
not limited to, at least one of a poly(vinyl alcohol), gel, gel
matrix, hydrogel, or azopolymer membrane. For example, a poly(vinyl
alcohol) is described in (S. P. Vijayalakshmi, et al.,
Photodegradation of poly(vinyl alcohol) under UV and pulsed-laser
irradiation in aqueous solution, JOURNAL OF APPLIED POLYMER
SCIENCE, Vol. 102, No. 2, 958-966, 2006). For example, photo
responsive polymers, including using an azopolymer with laser
holography to generate the gated layer, are described in (J. Kyoo
Lee, et. al., Photo-Triggering of the Membrane Gates in
Photo-Responsive Polymer for Drug Release, ENGINEERING IN MEDICINE
AND BIOLOGY SOCIETY, (27th Annual International Conference) 2005
Pages: 5069-5072 (2005). In an embodiment, the release element
includes a photo-labile bond between a molecule of the medicament
190 and a bioactivity inhibiting molecule that is configured in a
first medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure of the labile bond to the
stimulus. Examples of such a photo-labile bond are described in M.
Scwarcznski, et al., Development of first photo responsive prodrug
of paclitaxel, 16 BIOORGANIC & MEDICAL CHEMISTRY LETTERS, Issue
17 4492-4496 (September 2006): Epub 27 Jun. 2006. Scwarcznski, et
al., describe synthesization of a prodrug of paclitaxel which has a
coumarin derivative conjugated to the amino acid moiety of isotaxel
(O-acyl isoform of paclitaxel). The prodrug was selectively
converted to isotaxel by visible light irradiation (430 nm) with
the cleavage of coumarin. Finally, paclitaxel was released by
subsequent spontaneous O--N intramolecular acyl migration.
[0103] In addition, the release element may include at least one of
an additional appropriate photodegradable/or biocompatible barrier
forming material.
[0104] In an embodiment, the release element 130 includes a release
element configured in a first medicament-release state and
modifiable ex vivo to a second medicament-release state by an
exposure to an energetic stimulus, also illustrated as stimulus
192. In an embodiment, an energetic stimulus may include at least
one of a mechanical stimulus, a non-ionizing radiation stimulus, an
ionizing radiation stimulus, a chemical stimulus, an acoustic
stimulus, an ultrasound stimulus, a radio wave stimulus, a
microwave stimulus, a light wave stimulus, or a thermal
stimulus.
[0105] In an embodiment, the release element 130 is configured in a
first medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure to at least one of
terahertz radiation, microwave radiation, and radio wave radiation,
also illustrated as the stimulus 192. For example, radio wave
radiation may include, for example, at least one of ultra-high
frequency radio waves (UHF), very high frequency radio waves (VHF),
radio frequency (RF), or extremely low frequency (ELF) radio waves.
In an embodiment, the release element 130 includes at least one of
a foil, gold foil, a liposome, wax, dielectric/wax composite. An
example of a microwave responsive liposome is described in U.S.
Pat. No. 4,801,459 to R. Liburdy. An example of a microwave
responsive material, including a wax and a wax/dielectric
composite, is described in United States Patent Application
Publication No. 2005/0191708 to R. Saul, et al. In an embodiment,
the release element is configured in a first medicament-release
state and modifiable ex vivo to a second medicament-release state
by an exposure to a magnetic stimulus. In an embodiment, the
release element is configured in a first medicament-release state
and modifiable ex vivo to a second medicament-release state by an
exposure to an electric field stimulus.
[0106] In an embodiment, the release element is configured in a
first medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure to a chemical stimulus (not
shown). For example, a chemical stimulus may include at least one
of a stimulus based on pH change, enzymatic exposure or catalysis.
In an embodiment, a chemical stimulus may include a stimulus
operable to release or reverse a cooperative or a reversible
molecular binding, or a stimulus operable to form an irreversible
binding.
[0107] In an embodiment, the release element 130 is configured in a
first medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure to a mechanical agitation
stimulus (not shown). For example, a mechanical agitation stimulus
may include a shaking or spinning to rupture a membrane or a seal
or a foil. In an embodiment, a release element is configured in a
first medicament-release state and modifiable ex vivo to a second
medicament-release state by an ex vivo exposure to a mechanical
stimulus (not shown). For example, a mechanical stimulus may
include shaking a piercing member against a foil release element.
In an embodiment, the release element is configured in a first
medicament-release state and modifiable ex vivo to a second
medicament-release state by an ex vivo exposure to the stimulus,
the release element including a mechanically activatable structure
(not shown). For example, the mechanically activatable structure
may include a foil or a pressure-rupturable membrane, or a
heat-activatable structure.
[0108] In an embodiment, the release element 130 is permeated,
dissolved, or disintegrated in response to the stimulus. In an
embodiment, a release element is changed such that it is permeated,
dissolved, or disintegrated in response to an in vivo environment
of the animal 198 where it would not have been so before exposure
to the stimulus. In an embodiment, a release element is changed
such that it forms a barrier, or is impermeable, solid, or integral
in response to the exposure to the stimulus where it would not have
been so before the exposure to the stimulus.
[0109] In an embodiment, the release element 130 is configured in a
first medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure to at least one of a
thermal, acoustic stimulus and ultrasound. Examples of an
acoustically active release element formed by conjugating liposomes
and microbubbles are described in A. Kheirolomoom, et al.,
Acoustically-active microbubbles conjugated to liposomes:
Characterization of a proposed drug delivery vehicle, 118 J CONTROL
RELEASE, Issue 3, April 23; 118(3):275-284. Epub 2006 Dec. 23.
[0110] In an embodiment, the release element 130 includes a release
element configured in a first medicament-release state and
modifiable ex vivo to a second medicament-release state by an ex
vivo exposure to at least one of an activation stimulus, or an
actuation stimulus. In an embodiment, the release element is
configured in a first medicament-release state and modifiable ex
vivo to a second medicament-release state by an exposure to a
de-activation stimulus.
[0111] In an embodiment, the release element 130 includes a release
element configured in a first medicament-release state and
modifiable ex vivo to a second medicament-release state by an
exposure to an ultrasound stimulus. For example, the release
element may include at least one of liposomes, lipid microspheres,
microbubbles, lipospheres, or liposomes responsive to an ultrasound
stimulus, which are described in U.S. Pat. No. 6,416,740 to Unger.
In an embodiment, the release element includes at least one of
polyanhidrides, polyglycolides, polyactides, poly(vinyl acetate),
poly(glycolic acid), poly(ethylene), poly(lactic acid), or
chitosan. An example of ultrasound-responsive polymer is described
in J. Kost, et al., Ultrasound-enhanced polymer degradation and
release of incorporated substances, 86 PROCEEDINGS OF THE NATIONAL
ACADEMY OF SCIENCES OF THE USA, 7663-7666 (1989). In this article,
Kost describes up to a 5-fold reversible increase in degradation
rate and up to 20-fold reversible increase in release rate of
incorporated molecules were observed with biodegradable
polyanhydrides, polyglycolides, and polylactides. This article also
describes up to a 10-fold reversible increase in release rate of
incorporated molecules within nonerodible ethylene/vinyl acetate
copolymer were also observed. The release rate increased in
proportion to the intensity of ultrasound. Temperature and mixing
were relatively unimportant in effecting enhanced polymer
degradation, whereas cavitation appeared to play a significant
role. Another example of ultrasound-responsive polymer is described
in J. Kost, et al., Ultrasonically controlled polymeric drug
delivery, Makromolekulare Chemie 19 MACROMOLECULAR SYMPOSIA 275-285
(1988). In this article, Kost describes investigation of polymers
that include lactic acid polymer, glycolic acid polymer, ethylene
copolymer, vinyl acetate copolymer. An example of
ultrasound-responsive chitosan is described in M. Tsaih, et al.,
Effect of the degree of deacetylation of chitosan on the kinetics
of ultrasonic degradation of chitosan; 90 JOURNAL OF APPLIED
POLYMER SCIENCE 3526-3531 (2003).
[0112] In an embodiment, the release element 130 includes at least
one of polymeric micelle, liposome, lipid microsome, polymeric
microsphere, nanoparticle, clathrate compound, cyclodextrin, gel,
gel matrix, hydrogel, or cellulose. Examples of polymeric micelles
are described in U.S. Pat. No. 7,229,973 to Bae, et al. Bae
describes polymeric micelles including mixed micelles containing
poly(L-histidine)-poly(ethylene glycol) block copolymer and
poly(L-lactic acid)-poly(ethylene glycol) block copolymer. Examples
of polymer microspheres are described in U.S. Pat. No. 5,718,921 to
Mathiowitz, et al. Mathiowitz describes polymer microspheres built
using polyanhydrides, polyorthoesters, polylactic acid polymers,
and combinations thereof. Examples of cyclodextrin are described in
U.S. Pat. No. 7,270,808 to Cheng, et al., titled
"Cyclodextrin-based polymers for therapeutics delivery." Examples
of hydrogels are described in Lin et al., Hydrogels in controlled
release formulations: Network design and mathematical modeling,
ADVANCED DRUG DELIVERY REVIEWS 58 (2006) 1379-1408). Examples of
cellulose are described in U.S. Pat. No. 6,821,531 to Kumar.
[0113] In an embodiment, the release element 130 includes a release
element enclosing the chamber 120, configured in a first
medicament-release state, and modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus, illustrated
as the stimulus 192. For example, FIG. 1 illustrates an embodiment
where the outer layer 110 has a spherical shape, the chamber may
have similar nested spherical shape, and the release element having
a spherical shape and surrounding the chamber. However, nothing in
this document expresses or implies a required similarity of shape
among one or more of the chamber, the release element, or the outer
layer. For example, an embodiment may include a liposome forming
the release element and functionally defining a chamber.
[0114] In an embodiment, the release element 130 includes or
defines a release element encapsulating the chamber. In an
embodiment, the release element includes a release element
encapsulating the medicament 190 in cooperation with the chamber
wall 122, configured in a first medicament-release state, and
modifiable ex vivo to a second medicament-release state by an
exposure to the stimulus. For example, FIG. 2, infra, illustrates a
release element 230 encapsulating the medicament 190 in cooperation
with a chamber 220 as expressed or defined by a chamber wall 222.
In an embodiment, the release element includes a release element
obstructing an aperture of the chamber. For example, FIG. 3, infra,
illustrates a release element 330 in cooperation with a chamber 320
as expressed by a chamber wall 322 obstructing an aperture 332 of
the chamber and preventing a discharge of the medicament 190 along
a fluid communication path 336 In an embodiment, the release
element includes at least two particles each collectively or
respectively forming a chamber carrying a respective instance of
the medicament. For example, FIG. 4, infra, illustrates a release
element 430 that includes a particle 432 forming a chamber carrying
an instance of the medicament 190. An example of the particle 432
is additionally described in conjunction with FIGS. 16, 20, and 23,
and respective corresponding particle or polymeric material 1180,
1580, and 1680. The particle is configured in a first
medicament-release state, and modifiable ex vivo to a second
medicament-release state by an exposure of the at least two
particles to the stimulus. For example, the particle may include a
clathrate compound forming a host/guest relationship with molecules
of a medicament. For example, the particle may include at least one
of hydrogels, liposomes, or dendrimers configured to carry the
medicament in an association with their pores, interstitial
cavities, structural interstices, bonds, or amorphous cavities.
[0115] In an embodiment, the release element includes a labile bond
between a molecule of the medicament and a bioactivity inhibiting
molecule configured in a first medicament-release state and
modifiable ex vivo to a second medicament-release state by an
exposure of the labile bond to the stimulus (not shown).
[0116] Referring again to FIG. 1, in an embodiment, the release
element 130 is configured in a first medicament-release state and
modifiable ex vivo to a second medicament-release state by an
exposure to the stimulus, and configured to contain the medicament
190 at least until the final dosage form 102 is administered into
the animal 198.
[0117] FIG. 1 illustrates an embodiment having the chamber 120
formed within the outer layer 110 and configured to carry the
medicament 190. In an embodiment, the chamber 120 is substantially
defined within the outer layer and configured to carry the
medicament until released by the release element. For example, FIG.
2 illustrates an embodiment that includes the chamber 220
substantially defined within the outer layer 210 and configured to
carry the medicament 190 until released by the release element 230.
FIG. 3 illustrates an embodiment that includes the chamber 320
substantially defined within the outer layer 310 and configured to
carry the medicament 190 until released by the release element
330.
[0118] In an embodiment (not shown), the release element and
chamber both may be formed by a particle, such as a liposome, or a
hydrogel. In such embodiment, the chamber includes at least one
chamber substantially within the outer layer of the particle and
configured to carry the medicament.
[0119] In an embodiment, the chamber 120 includes a chamber
configured to confine the medicament 190 in cooperation with the
release element 130. In an embodiment (not shown), the chamber
includes at least one chamber configured to confine the medicament
in a structural cooperation with the release element. In an
embodiment (not shown), the chamber is configured to initially
carry the medicament. The chamber is also configured to release at
least a portion of the medicament upon at least one of a
reconfiguration, bursting, puncture, permeation, dissolution, and
disintegration of the release element 130.
[0120] In an embodiment (not shown), the chamber 120 includes a
first chamber configured to carry a first medicament and a second
chamber configured to carry a second medicament. An example of the
first chamber configured to carry a first medicament and the second
chamber configured to carry a second medicament is described in
conjunction with FIG. 5 and chamber 520A and chamber 520B. In an
embodiment (not shown), the chamber includes a first chamber
configured to carry a first constituent of the medicament and a
second chamber configured to carry a second constituent of the
medicament. In an embodiment (not shown), the chamber includes a
first chamber configured to carry a first reactant of the
medicament and a second chamber configured to carry a second
reactant of the medicament. In an embodiment (not shown), a
combination of the first reactant and the second reactant in
response to an ex vivo exposure of the release element initiates a
chemical activation or a synthesis of the medicament and a physical
releasability of the medicament. In an embodiment (not shown), a
combination of the first reactant and the second reactant in
response to an ex vivo exposure of the release element initiates a
chemical activation or a synthesis of the medicament but does not
provide a physical releasability of the medicament. In an
embodiment, the resulting medicament product can be released in
vivo through the release characteristics of the outer layer.
Alternatively, the physical releasability of the medicament may
occur by another ex vivo exposure of the dosage form to a stimulus,
such as the stimulus 192.
[0121] In an embodiment shown in FIG. 1, the final dosage form 102
includes a containment element 140 retaining the medicament 190
within the final dosage form until the dosage form is administered
to the animal 198. The containment element can be used in
situations where the medicament is a liquid or other material that
is prone to seepage or discharge through the outer layer. In
embodiment, the containment element may include a separate
structure, such as a film or coating, retaining the medicament.
Such a containment element 140 may form an exterior layer over the
outer layer 110, or may form a layer interposed between the outer
layer 110 and the chamber 120. In an embodiment, the containment
element 140 may inhibit a discharge of the medicament 190 from the
final dosage form 102 prior to its introduction into the animal
198, without regard to whether the release element is in its first
medicament-release state or its second medicament-release state. In
an embodiment, the containment element 140 includes a containment
element 140 retaining the medicament 190 within the final dosage
form 102 until the final dosage form 102 is exposed to an in vivo
environment in the animal 198, and to modulate a release of at
least a portion of the medicament 190 in vivo upon administration
of the final dosage form 102 to the animal 198. In an embodiment,
the containment element may be formed by a combination of the outer
layer 110 and the release element 130.
[0122] In an embodiment, the containment element 140 includes a
containment layer configured to encompass the medicament 190 within
the final dosage form 102 until the final dosage form is
administered to the animal 198. For example, the containment
element 140 may include a coating covering the outer layer 110 of
the final dosage form 102, such as an enteric coating configured to
prevent a release of the medicament from the final dosage form
until the final dosage form is administered to the animal. In
another example, the containment element 140 may include a coating
covering the release element 130 of the final dosage form 102. In
an embodiment, the containment element includes a containment
envelope retaining the medicament within the final dosage form
until the dosage form is administered to the animal.
[0123] In an embodiment, the containment element 140 includes an
enteric coating. The enteric coating may include gelatin or
cellulose encapsulation. In an embodiment, the containment element
includes a hydroxypropyl methylcellulose acetate succinate (HPMCAS)
based coating or a methacrylic acid copolymer based coating, for
example such as described in U.S. Pat. No. 7,138,143 to Mukai, et
al. In an embodiment, the containment element includes a polymer
coating, such as an acidic group-containing (meth)acrylate
copolymer, shellac, HPMCP (hydroxypropylmethylcellulose phthalate),
CAP (cellulose acetate phthalate), HIPMC-AS
(hydroxypropylmethylcellulose acetate succinate) or polyvinyl
acetate phthalate, for example such as described in U.S. Pat. No.
6,887,492 to Kay, et al. In an embodiment, the containment element
includes a polymer coating of a (meth)acrylate copolymer comprising
free-radical polymerized C.sub.1- to C.sub.4-alkyl esters of
acrylic or methacrylic acid and (meth)acrylate monomers with a
quaternary anunonium group in the alkyl radical, a (meth)acrylate
copolymer of 20 to 40% by weight of polymerized ethyl acrylate and
60 to 80% by weight of polymerized methyl methacrylate,
ethylcellulose or polyvinyl acetate. For example, as described in
U.S. Pat. No. 6,897,205 to Beckert et al. In an embodiment, the
containment element includes a cellulose acetate phthalate polymer
coating material, for example, as described in U.S. Pat. No.
5,686,106 to Kelm, et al. In an embodiment, the containment element
includes a cellulose acetate phthalate; cellulose acetate
trimellitate; hydroxypropyl methylcellulose phthalate;
hydroxypropyl methylcellulose acetate succinate; polyvinyl acetate
phthalate; poly(methacrylic acid, methyl methacrylate) 1:1; or
poly(methacrylic acid, ethyl acrylate) 1:1; and compatible mixtures
thereof. In another embodiment, the containment element includes a
poly(methacrylic acid, methyl methacrylate) 1:2, or a mixture of
poly(methacrylic acid, methyl methacrylate) 1:1 and
poly(methacrylic acid, methyl methacrylate) 1:2 in a ratio of about
1:10 to about 1:2. For example, as described in U.S. Pat. No.
5,686,105 to Kelm, et al.
[0124] In an embodiment illustrated in FIG. 2 infra, the
containment element 240 includes a containment element 240
configured to prevent a release of the medicament 190 from the
final dosage form 202 until the final dosage form 202 is introduced
into the animal 198.
[0125] Returning to FIG. 1, in an embodiment, the medicament 190
includes at least one of an agent, treatment agent, drug, prodrug,
therapeutic, nutraceutical, medication, vitamin, nutritional
supplement, medicine, remedy, medicinal substance, or cosmetic. In
an embodiment, the medicament includes a first reactant of the
medicament and a second reactant of the medicament. In an
embodiment, the medicament includes at least one prodrug and
optionally an activating-enzyme of the prodrug. In an embodiment,
the chamber includes a first chamber configured to carry a prodrug,
and a second chamber configured to carry an activating enzyme of
the prodrug.
[0126] In an embodiment, the final dosage form 102 may further
include a indicator element 180 configured to indicate an exposure
of the release element 130 to the stimulus 192. In an embodiment,
the indicator element 180 includes an indicator element 180
configured to optically indicate an exposure of the release element
to the stimulus 192 by at least one of dielectric, a conductivity,
or ultrasonic profile responsive to an exposure of the release
element to the stimulus. The indicator element 180 including, for
example, at least one of 4-keto-bacteriorhodopsin films,
cinnamylidene acetyl chloride, .alpha.-methylcinnamylidene acetyl
chloride, .alpha.,.gamma.-dimethylcinnamylidene acetyl chloride,
.alpha.-phenylcinnamylidene acetyl chloride,
.alpha.-phenoxycinnamylidene acetyl chloride, and
cyanocinnamylidene acetyl chloride, leuco dye-serum albumin albumin
complexes, azo dyes, or poly(ethylene glycol). Examples of
bacteriorhodopsin films are described in A. Druzhko, et al.,
4-Keto-bacteriorhodopsin films as a promising photochromic and
electrochromic biological material, BIOSYSTEMS. 1995; 35(2-3):
129-32. Examples of hydrophilic photosensitive polymers are
described in U.S. Pat. No. 5,990,193 to Russell, et al. Examples of
photosensitive compositions for detection of radiation in the
ultraviolet wavelength, including leuco dye-serum albumin
complexes, are described in U.S. Pat. No. 4,466,941 to Cerami, et
al. Examples of using azo dye for an indicator is described in U.S.
Pat. No. 5,679,442. Examples of poly(ethylene glycol) are described
in U.S. Pat. No. 5,990,193 to Russell, et al., and in Zhong, et
al., Photodegradation Behavior of Polycaprolactone-Poly(ethylene
glycol) Block Copolymer, Vol. 10, No. 4 CHINESE CHEMICAL LETTERS
327-330 (1999).
[0127] In an embodiment depicted in FIG. 1, the indicator element
180 includes an electronically-detectable indicator element 180
configured to indicate an exposure of the release element 130 to
the stimulus 192. For example, the electronically-detectable
indicator element 180 may include a substance, material, or device
having a conductive property that makes an
electronically-detectable change in response to an exposure to the
stimulus 192. An example of such substance, material, or device
includes a shape memory alloy switch that responds to heat
described in U.S. Pat. No. 5,410,290 to Cho. Other examples of such
substances, materials, or devices include a material that
polymerizes in the presence of an ultrasound and changes a
conductive property in response, such as the ultrasonic
polymerization of methyl methacrylate described in U.S. Pat. No.
5,466,722 to Stoffer, et al., the heat or UV radiation triggered
polymerization of acrylamide, or the microwave triggered
polymerization of trimethylene carbonate. Another example of such
substances, materials, or devices include the use of bistable
compounds whose conductivity changes based upon exposure to
electromagnetic radiation as described in U.S. Pat. No. 7,175,961
to Beck, et al. Another example includes a metal film or foil
degradable by microwaves to release the medication whose state can
degradation detected electrically.
[0128] In an embodiment, the indicator element 180 includes an
electronically-detectable indicator element 180 configured to
indicate an exposure of the release element 130 to the stimulus
192. For example, the electronically-detectable indicator element
180 may include a dielectric element having a property that makes
an electronically-detectable change in response to an exposure to
the stimulus 192. An example of such a dielectric element may
include a one-time programmable memory cell described in U.S. Pat.
No. 7,256,446, to Hu, et al., or a switch comprising
microelectromechanical elements described in U.S. Pat. No.
7,336,474 to Lerche, et al.
[0129] In an example, the electronically-detectable indicator
element 180 may include an element having a permittivity that makes
an electronically-detectable change in response to an exposure of
the release element to the stimulus 192. An example of such an
element having a permittivity may include photonic crystals whose
permittivity changes through the addition of photonic and/or
electrical energy as described in U.S. Pat. No. 6,859,304 to
Miller, et al.
[0130] In another example, the electronically-detectable indicator
element 180 may include an element having an ultrasonic profile
that makes an ultrasound-discernable change in response to an
exposure of the release element to the stimulus 192. An example of
an element having an ultrasonic profile that includes a polymer
monitorable using the continuous wave ultrasonic process monitor is
described in U.S. Pat. No. 7,017,412 to Thomas, et al. Another
example of an element having an ultrasonic profile that includes a
polymer monitorable using the apparatus for degree on doneness is
described in U.S. Pat. No. 7,191,698 to Bond, et al. A further
example of an element having an ultrasonic profile that includes a
degradable metal film or metal foil.
[0131] In another example, the electronically-detectable indicator
element 180 may include a carrier, admixture, diluent, or excipient
having a property that makes an ultrasound-discernable change in
response to an exposure of the release element to the stimulus 192.
For example, an admixture may include a phase change material (PCM)
as an inert filler and having a property that makes an
ultrasound-discernable change in response to an exposure of the
release element to ultrasound. Examples of such PCMs include
polyvinyl alcohol (PVA)-stearic acid (SA) and polyvinyl chloride
(PVC)-stearic acid (SA). An example of Polymer-stearic acid blend
is described in Ahmet Sari, et al., Polymer-stearic acid blends as
form-stable phase change material for thermal energy storage, 64
JOURNAL OF SCIENTIFIC & INDUSTRIAL RESEARCH, at pp. 991-996
(December 2005). Other examples are described in United States
patent application No. 2007/0249753 to Lin, et al. (polyether
fatty-acid ester (polyethylene glycol or polytetramethylene glycol
base polymer), and U.S. Pat. No. 5,565,132 to Salyer (Addition of
microwave absorber to make PCM materials sensitive to microwaves).
Ultrasonic detection or discernment of phase changes in a PCM may
be implemented using techniques described by A. W. Aziz, & S.
N. Lawandy, Ultrasonic detection of segmental relaxations in
thermoplastic polyurethanes, 31 JOURNAL OF APPLIED POLYMER SCIENCE
1585 (Issue 6, 2003) or S. L. Morton, Ultrasonic cure monitoring of
photoresist during pre-exposure bake process, ULTRASONICS
SYMPOSIUM, 1997. PROCEEDINGS. 1997 IEEE Volume 1, at 837-840
(October 1997).
[0132] The indicator element 180 (as enumerated in FIG. 1) can be
made biocompatible so as to not cause an adverse reaction in the
animal. Biocompatibility can be achieved through the use of a
biocompatible material or through the use of a minimal amount of
material so that any adverse reaction to the indicator element 180
is minimized.
[0133] FIG. 2 illustrates an environment 200 that includes the
animal 198, a cross-sectional view of an example final dosage form
202 for administering the medicament 190 to the animal, and the
example stimulation source 194 operable to emit the stimulus 192.
In an embodiment, the final dosage form includes a dosage form
having completed a manufacturing or production process. In an
embodiment, the final dosage form includes a product, finished
tablet, or capsule ready for distribution to a hospital, pharmacy,
or retail store for individualizing to a particular animal, such as
the animal 198. In an embodiment, the final dosage form may include
a tablet shape, a spherical shape, or an ellipsoidal shape. In an
embodiment, the final dosage form may include a structure or a
particle carryable or transportable by a liquid or other fluid
carrier.
[0134] The final dosage form 202 includes an outer layer 210, the
release element 230, and the chamber 220 as expressed or defined by
the chamber wall 222. The release element is configured in a first
medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus. For example,
the stimulus may include the stimulus 192. The chamber includes a
chamber wall 222, is substantially within the outer layer, and is
configured to carry the medicament 190. In an embodiment, the final
dosage form may include an indicator element 280. In an embodiment,
the final dosage form may include a containment element 240.
[0135] The environment 200 illustrates an embodiment where the
release element 230 encompasses the medicament 190 in cooperation
with the chamber 220 as expressed or defined by the chamber wall
222. The outer layer 210 and the release element 230 are
cooperatively retaining the medicament 190 if the release-element
is in a first medicament-release state and allow an in vivo
discharge of at least a portion of the medicament from the chamber
if the release-element is in a second medicament release state. In
an embodiment, the release element may include at least one of a
poly(vinyl alcohol), gel, gel matrix, hydrogel, and azopolymer
photo or light modifiable substance as described above. In an
embodiment, the release element may include at least one of a
polyanhidride, polyglycolide, polyactide, poly(vinyl acetate),
poly(glycolic acid), poly(ethylene), poly(lactic acid), chitosan,
or an acoustic or ultrasound-modifiable substance as described
above. For example, when the first medicament-release state is
configured to retard medicament release and the second
medicament-release state is configured to allow medicament release
in vivo, the release element when configured in the first
medicament-release state will retard medicament release from the
final dosage form upon administration of the final dosage form into
the animal. For example, in a first medicament release state, the
release element is impermeable to the environment outside the final
dosage form, and impermeable to the medicament in the chamber.
Following exposure to an appropriately configured stimulus, the
release element achieves a second medicament release state that is,
for example, permeable to the medicament. The second medicament
release state may include, for example, a state where the release
element changes shape or size (e.g., expands, shrinks), dissolves,
or dissipates upon exposure to an aqueous environment, gastric
juices or a certain pH environment.
[0136] FIG. 3 illustrates a non-limiting environment 300 that
includes the animal 198, a cross-sectional view of an example final
dosage form 302 for administering the medicament 190 to the animal,
and the example stimulation source 194 operable to emit the
stimulus 192. In an embodiment, the final dosage form includes a
dosage form having completed a manufacturing or production process.
In an embodiment, the final dosage form includes a product,
finished tablet, or capsule ready for distribution to a hospital,
pharmacy, or retail store for individualizing to a particular
animal, such as the animal 198. In an embodiment, the final dosage
form may include a tablet shape, a spherical shape, or an
ellipsoidal shape. In an embodiment, the final dosage form may
include a structure or a particle carryable or transportable by a
liquid or other fluid carrier.
[0137] The final dosage form 302 includes an outer layer 310, a
chamber 320, and a release element 330. The final dosage form also
includes a release passageway 332 configured to provide a
medicament communication pathway between the chamber and the
environment through an aperture 334 in the outer layer. The release
element is configured in a first medicament-release state and
modifiable ex vivo to a second medicament-release state by an
exposure to a stimulus. For example, the stimulus may include the
stimulus 192. The chamber includes a chamber wall 322, is
substantially within the outer layer, and is configured to carry
the medicament 190. In an embodiment, the final dosage form may
include an indicator element 380. In an embodiment, the final
dosage form may include a containment element 340.
[0138] FIG. 3 illustrates a non-limiting embodiment wherein an
embodiment of the final dosage form 302 includes the release
element 330 retaining the medicament 190 in cooperation with the
chamber 320 as expressed by the chamber wall 322. The outer layer
310 and the release-element 330 are cooperatively retaining the
medicament 190 if the release-element is in one medicament-release
state and allowing an in vivo discharge of at least a portion of
the medicament from the chamber if the release-element is in
another medicament release state. When the release-element is in a
state that releases the medicament, the medicament may discharge or
flow along the fluid communication path 336 expressed or defined at
least in part by the release passageway 332.
[0139] In an embodiment, the release element may include at least
one of a poly(vinyl alcohol), gel, gel matrix, hydrogel, and
azopolymer photo or light modifiable substance as described above.
In an embodiment, the release element may include at least one of a
foil, gold foil, wax, or dielectric/wax composite microwave
modifiable substance. In an embodiment of this example, the release
element may include at least one of a polyanhidride, polyglycolide,
polyactide, poly(vinyl acetate), poly(glycolic acid),
poly(ethylene), poly(lactic acid), chitosan, or an acoustic or
ultrasound-modifiable substance as described above. For example,
when the first medicament-release state is configured to retard
medicament release and the second medicament-release state is
configured to allow medicament release in vivo, the release element
when configured in the first medicament-release state will retard
medicament release from the release passageway 332 and the aperture
334 of the final dosage form upon administration of the final
dosage form into the animal.
[0140] FIG. 4 illustrates an environment 400 that includes the
animal 198, a cross-sectional view of an example final dosage form
402 for administering the medicament 190 to the animal, and the
example stimulation source 194 operable to emit the stimulus 192.
In an embodiment, the final dosage form 402 includes a dosage form
having completed a manufacturing or production process. In an
embodiment, the final dosage form 402 includes a product, finished
tablet, or capsule ready for distribution to a hospital, pharmacy,
or retail store for individualizing to a particular animal, such as
the animal 198. In an embodiment, the final dosage form 402 may
include a tablet shape, a spherical shape, or an ellipsoidal shape.
In an embodiment, the final dosage form 402 may include a structure
or a particle carryable or transportable by a liquid or other fluid
carrier.
[0141] The final dosage form 402 includes an outer layer 410, a
chamber 420, and a release element 430. The release element is
configured in a first medicament-release state and modifiable ex
vivo to a second medicament-release state by an exposure to a
stimulus. For example, the stimulus may include the stimulus 192.
The chamber includes a chamber wall 422, is substantially within
the outer layer, and is configured to carry the medicament 190. In
an embodiment, the final dosage form 402 may include an indicator
element 480. In an embodiment, the final dosage form 402 may
include a containment element 440.
[0142] In an embodiment, the chamber 420 includes a chamber
substantially within the outer layer 410 and configured to carry
the medicament 190. In an embodiment, the chamber encloses at least
two structures within the chamber having respective subchambers
configured to carry the medicament. For example, such at least two
structures may include at least two pores, molecular structures
having interstitial cavities, smaller chambers, molecular structure
having interstices, or molecular structure having amorphous
cavities. In an embodiment, the chamber may contain at least one of
an absorbent, liposome, or hydrogel molecular structure which
define respective chambers therein. For example, at least two
particles may be located in a cavity, such as the chamber 120, and
in themselves define a distributed chamber by an aggregation of
their pores, interstitial cavities, smaller chambers, interstices
of a molecular structure, or amorphous cavities. In another
example, at least two microparticles may be throughout a carrier
having an outer layer, each microparticle having an effective
chamber. In an embodiment, the chamber is located substantially
within the release element 430. In an embodiment, the distributed
chamber is located substantially within the outer layer 410.
[0143] The final dosage form 402 may include a release element 430
that is associated with the medicament 190 in the chamber 420. In
an embodiment, the release element 430 may include a carrier,
admixture, diluent, or excipient configured in a first
medicament-release state and modifiable ex vivo to a second
medicament-release state by an ex vivo exposure to the stimulus
192. Particles of such a carrier, admixture, diluent, or excipient
may be configured to retain or bind to particles of the medicament
190 and reduce its bioavailability if the release-element 430 is in
a first medicament-release state, and release from or unbind
particles of the medicament 190 and allow an in vivo discharge of
at least a portion of the medicament 190 from the chamber 420 if
the release-element 430 is in a second medicament release
state.
[0144] In an embodiment, an instance of the final dosage form 402
may carry at least two particles, small particles, or
microparticles that each include a portion that forms a release
element 430 modifiable ex vivo by exposure to the stimulus 192, and
a chamber (not shown). The chambers of the at least two particles,
small particles, or microparticles each configured to carry a
respective instance of the medicament, and collectively forming a
distributed chamber. For example, the at least two particles, small
particles, or microparticles may include hydrogels, liposomes, or
dendrimers having pores, interstitial cavities, structural
interstices, bonds, or amorphous cavities configurable to carry
molecules of the medicament. The at least two particles, small
particles, or microparticles are configured in a first
medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure of the at least two
particles, small particles, or microparticles to the stimulus. For
example, photosensitive hydrogel particles may carry the
medicament. In an embodiment, microwave sensitive liposomes may
carry the medicament. In an embodiment, the release element
includes a labile bond between a molecule of the medicament and
molecule of a bioactivity inhibiting molecule configured in a first
medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure of the labile bond to the
stimulus (not illustrated).
[0145] FIG. 5 illustrates an environment 500 that includes the
animal 198, a cross-sectional view of a final dosage form 502 for
transporting a medicament to the animal. The medicament is
illustrated as a first medicament 190A and second medicament 190B.
In an embodiment, the final dosage form includes a dosage form
having completed a manufacturing or production process. In an
embodiment, the final dosage form 502 includes a product, finished
tablet, or capsule ready for distribution to a hospital, pharmacy,
or retail store for individualizing to a particular animal, such as
the animal 198. In an embodiment, the final dosage form 502 may
include a tablet shape, a spherical shape, or an ellipsoidal shape.
In an embodiment, the final dosage form 502 may include a structure
or a particle carryable or transportable by a liquid or other fluid
carrier.
[0146] The final dosage form 502 includes an outer layer 510, and
at least two dosage elements. The at least two dosage elements are
illustrated as A Portion and B Portion, and by "A" and "B" after
certain reference numbers in FIG. 5. The A Portion includes a
chamber 520A, a release element 530A, and a medicament 190A. In an
embodiment, the A Portion includes a containment element 540A. In
an embodiment, the A Portion includes an indicator element 580A.
The B Portion includes a chamber 520B, a release element 530B, and
a medicament 190B. In an embodiment, the B Portion includes a
containment element 540B. In an embodiment, the B Portion includes
an indicator element 580B.
[0147] In an embodiment, the A Portion of the final dosage form 502
may be substantially similar to the chamber 120, the release
element 130, the containment element 140, and the indicator element
180 of FIG. 1. In an embodiment, the A Portion may be substantially
similar to the chamber 220, the release element 230, the
containment element 240, and the indicator element 280 of FIG. 2.
In an embodiment, the A Portion may be substantially similar to the
chamber 320, the release element 330, the containment element 340,
and the indicator element 380 of FIG. 3. In an embodiment, the A
Portion may be substantially similar to the chamber 420, the
release element 430, the containment element 440, and the indicator
element 480 of FIG. 4. Similarly, the B Portion of the final dosage
form 502 may be substantially similar to that described in
conjunction with at least one of FIG. 1, FIG. 2, FIG. 3, or FIG.
4.
[0148] In an embodiment, the first medicament 190A and the second
medicament 190B may be substantially similar instances of the same
medicament. In an embodiment, the first medicament 190A and the
second medicament 190B may be substantially similar instances of
the same medicament, but in substantially differing dosage amounts.
For example, the first medicament 190A may be, for example, a
50-milligram dose of a medicament and the second medicament 190B
may be, for example, a 100-milligram dose of the same medicament.
In an embodiment, the first medicament 190A and the second
medicament 190B may be substantially similar instances of the same
medicament, but in substantially differing dosage characteristics,
such as a regular release formulation and a sustained release
formulation. In an embodiment, the first medicament 190A and the
second medicament 190B may be different medicaments.
[0149] In use, the A Portion and the B Portion of the final dosage
form 502 may be individually or collectively exposed ex vivo to a
stimulus, illustrated as the stimulus 192. For example, the final
dosage form 502 can be configured to provide any of three possible
dosage levels of the medicament. For example, where the first
medicament 190A is a 50-milligram dose of a medicament and the
second medicament 190B is a 100-milligram dose of a same
medicament, where the release element 530A and release element 530B
are modifiable ex vivo by the same stimulus, such as microwave
energy, and where the first medicament-release state is configured
to retard medicament release in vivo and the second
medicament-release state is configured to allow medicament release
in vivo, irradiation of the A Portion with microwave energy will
actuate the A Portion and make 50-milligrams of the medicament
available upon administration of the final dosage form to the
animal 198. Similarly, irradiation of the B Portion with microwave
energy will actuate the B Portion and make 100-milligrams of the
medicament available upon administration of the final dosage form
to the animal. Further, irradiation of both the A Portion and the B
Portion with microwave energy will actuate both Portions and make
150-milligrams of the medicament available upon administration of
the final dosage form to the animal. In another example, the first
medicament 190A is a 100-milligram dose of a first medicament and
the second medicament 190B is a 100-milligram dose of a second
medicament. Selective irradiation of the A Portion or the B Portion
will make one or both of the medicaments bioavailable upon
administration of the final dosage form to the animal. In a further
example, the release element 530A is modifiable ex vivo by a first
stimulus and the release element 530B is modifiable ex vivo by the
second and different stimulus.
[0150] FIG. 6 illustrates an example environment 600 that includes
an article of manufacture 601. The article of manufacture includes
a package 660 containing a final dosage form 602 and providing an
instruction 670. The final dosage form includes a medicament 190,
an outer layer 610, a release element 630, and a chamber 620. The
release element is configured in a first medicament-release state
and modifiable ex vivo to a second medicament-release state by an
exposure to an actuation-stimulus. The chamber lies substantially
within the outer layer and is configured to carry the medicament.
The instruction includes instruction for preparation of the final
dosage form for an efficacious administration to an animal by an
exposure of the release element of the final dosage form to the
stimulus.
[0151] In an embodiment, the final dosage form 602 may be
substantially similar to the final dosage form 102 of FIG. 1. In an
embodiment, the final dosage form 602 may be substantially similar
to the final dosage form 202 of FIG. 2. In an embodiment, the final
dosage form 602 may be substantially similar to the final dosage
form 302 of FIG. 3. In an embodiment, the final dosage form 602 may
be substantially similar to the final dosage form 402 of FIG. 4. In
an embodiment, the final dosage form 602 may be substantially
similar to the final dosage form 502 of FIG. 5.
[0152] In an embodiment, the instruction 670 includes at least one
of information indicating an actuation-stimulus type, an
actuation-stimulus wavelength, an actuation-stimulus intensity, an
actuation-stimulus duration, a spatial distribution of the stimulus
relative to the final dosage form, a target-value for an exposure
indicator, or a combination thereof. For example, the information
indicating a spatial distribution of the stimulus relative to the
final dosage form may include information corresponding to aiming
the stimulus, such as toward a right hand portion, a center
portion, or a left hand portion of the final dosage form. In an
embodiment, the instruction includes an instruction presented by at
least one of a label (not shown) on the package 660, an insert in
the package, illustrated as the instruction 670, or an address to
electronically published content (not shown). In an embodiment, the
instruction includes instruction for preparation of the final
dosage form for an efficacious administration to an animal by a
human-initiated exposure of the release element of the final dosage
form to the actuation-stimulus.
[0153] In an embodiment, the final dosage form 602 further includes
a containment element 640 retaining the medicament within the final
dosage form until the final dosage form is introduced into the
animal. In an embodiment, the final dosage form includes an
indicator element 680 configured to indicate an exposure of the
release element to the stimulus. In an embodiment, the instruction
670 includes information indicating an expected value of the
indicator element.
[0154] FIG. 7 illustrates an example operational flow 700
modulating a medicament-release characteristic of a final dosage
form. A start operation occurs in an environment 705 that includes
the final dosage form. The final dosage form includes a medicament,
an outer layer, a release element configured in a first
medicament-release state and modifiable ex vivo to a second
medicament-release state by an exposure to the stimulus, and a
chamber substantially within the outer layer and configured to
carry the medicament. After the start operation, the operational
flow includes an individualization operation 710. The
individualization operation includes irradiating the release
element of the final dosage form ex vivo with a non ionizing
radiation, the non-ionizing radiation selected to transform the
release element from the first medicament-release state to the
second medicament-release state. For example, the irradiating the
release element of the final dosage form ex vivo with the stimulus
may occur in a hospital pharmacy, a retail pharmacy, a battlefield
hospital, a veterinary facility, or other location dispensing
medicaments. In another example, the irradiating a release element
of the final dosage form ex vivo with the stimulus may occur in a
persons home. The operational flow then proceeds to an end
operation. In an alternative embodiment, the final dosage form
further includes a containment element retaining the medicament
within the final dosage form before introduction of the final
dosage form into the animal.
[0155] FIG. 8 illustrates an alternative embodiment of the
operational flow 700 of FIG. 7. The individualization operation 710
may include at least one additional operation. The at least one
additional operation may include at least one of an operation 712,
an operation 714, an operation 716, an operation 718, or an
operation 722. The operation 712 includes irradiating in response
to a human-initiated activation a release element of the final
dosage form ex vivo with a non-ionizing radiation. The operation
714 includes automatically initiating an ex vivo irradiation with a
non-ionizing radiation a release element of the final dosage. The
operation 716 includes irradiating a first release element of the
final dosage form ex vivo with a non-ionizing radiation without
irradiating a second release element of the final dosage form with
the stimulus. The operation 718 includes irradiating a first
release element of the final dosage form ex vivo with a
non-ionizing radiation without irradiating a second release element
of the final dosage form with the non-ionizing radiation. The first
release element is associated with a first chamber carrying a first
instance of the medicament, and the second release element is
associated with a second chamber carrying a second instance of the
medicament. The operation 722 includes irradiating a first release
element of the final dosage form ex vivo with a non-ionizing
radiation without irradiating a second release element of the final
dosage form with the stimulus. The first release element is
associated with a first chamber carrying a first medicament, and
the second release element is associated with a second chamber
carrying a second medicament.
[0156] FIG. 9 illustrates an example operational flow 800
fulfilling a request specifying a dose of a medicament for an
individual animal. A start operation occurs in an environment that
includes a final dosage form. The final dosage form includes an
outer layer, a release element configured in a first
medicament-release state and changeable to a second
medicament-release state by an exposure to the stimulus, a chamber
substantially within the outer layer and configured to carry the
medicament, and the medicament. In an alternative embodiment, the
final dosage form further includes a containment element retaining
the medicament within the final dosage form before introduction of
the final dosage form into the animal. After the start operation,
the operational flow includes a picking operation 810. The picking
operation includes choosing pursuant to the request an instance of
a final dosage form that includes the medicament. A decision
operation 830 includes selecting a stimulus configured to change or
transform a medicament-release state of a release element of the
final dosage form. A customization operation 850 includes
initiating an exposure of the release element of the chosen
instance of the final dosage form to the selected stimulus. The
operational flow then proceeds to an end operation.
[0157] In use of an embodiment, a person such as a pharmacist
working in a pharmacy may receive a prescription specifying a dose
of a medicament for a patient. A pharmacy typically may have
available several different final dosage forms capable of
administering the prescribed medicament dose. For example, the
available different dosage forms may include at least one of the
embodiments of final dosage forms illustrated in FIGS. 1-5. In a
picking operation, the pharmacist chooses pursuant to the request
an instance of a final dosage form that includes the medicament. In
a decision operation, the pharmacist selects a stimulus effective
to change a medicament-release state of a release element of the
final dosage form. The pharmacist may select the stimulus after
consulting with an instruction presented by at least one of a label
on box containing the chosen instance of a final dosage form, a
package insert in the box, or an address to electronically
published content indicated on the label, or package insert. The
pharmacist enters the selected stimulus setting for a stimulus
emitter, such as the stimulus source 194 of FIG. 1. In a
customization operation, the pharmacist initiates an exposure of
the release element of the chosen instance of the final dosage form
to the selected stimulus. The pharmacist may confirm exposure of
the release element to the stimulus by referring to the indicator
element. For example, the indicator element may change color in
response to an exposure to the selected stimulus. If the
prescription specifies multiple doses of the medicament for the
patient, the pharmacist may repeat the above sequence until
sufficient doses have customized. Alternatively, and if appropriate
for the chosen final dosage forms, multiple instances of the final
dosage form may be ex vivo exposed to the selected stimulus at one
time.
[0158] FIG. 10 illustrates an alternative embodiment of the example
operational flow 800 of FIG. 9. The picking operation 810 may
include at least one additional operation. The at least one
additional operation may include an operation 812, or an operation
814. The operation 812 includes choosing pursuant to at least one
of an order or a prescription an instance of a final dosage form
that includes the medicament. The operation 814 includes at least
one of physically or manually choosing pursuant to the request an
instance of a final dosage form that includes the medicament.
[0159] FIG. 11 illustrates another embodiment of the example
operational flow 800 of FIG. 9. The decision operation 830 may
include at least one additional operation. The at least one
additional operation may include an operation 832, an operation
834, or an operation 836. The operation 832 includes selecting a
stimulus having an attribute indicated by at least one of a
manufacturer of the final dosage form, an instruction packaged with
the dosage form, an electronically published content, and a printed
publication as effective to change a medicament-release state of a
release element of the final dosage form. For example,
electronically published content may include a website maintained
by the manufacturer of the final dosage form. In a further example,
a printed publication may include a reference book, such as
Physician's Desk Reference. The operation 834 includes selecting a
stimulus configured by at least one of a type, amount, level,
wavelength, spectrum, waveform, spatial distribution, duration, or
pulse attribute to change a medicament-release state of a release
element of the final dosage form. The operation 836 includes
selecting a stimulus configured to change a medicament-release
state of a release element of the final dosage form and to make the
request-specified dose of medicament dose bioavailable by the final
dosage form.
[0160] FIG. 12 illustrates an embodiment of the example operation
800 of FIG. 9. The customization operation 850 may include at least
one additional operation. The at least one additional operation may
include an operation 852, an operation 854, or an operation 856.
The operation 852 includes changing a medicament-release state of
the release element of the chosen instance of the final dosage form
by initiating an exposure of the release element of the chosen
instance of the final dosage form to the selected stimulus. The
operation 854 includes preparing a bioavailable dose of the
medicament of the final dosage form in fulfillment of the request
by initiating an exposure of the release element of the chosen
instance of the final dosage form to the selected stimulus. The
operation 856 includes initiating an exposure of the release
element of the chosen instance of the final dosage form to the
selected stimulus in fulfillment of the request.
[0161] FIG. 13 illustrates an embodiment of the example operational
flow 800 of FIG. 9. The operation 870 may include at least one
additional operation. The at least one additional operation may
include an operation 872, an operation 874, or an operation 876.
The operation 870 may include at least one additional operation.
The at least one additional operation may include an operation 872,
an operation 874, or an operation 876. The operation 872 includes
optically verifying the exposure of the release element of the
chosen instance of the final dosage form to the selected stimulus.
For example, optically verifying the exposure may be implemented
using human vision, machine vision, or ultrasound techniques. The
operation 874 includes electronically verifying the exposure of the
release element of the chosen instance of the final dosage form to
the selected stimulus. For example, electronically verifying the
exposure of the release element may be implemented using a
dielectric element having a property that makes an electronically
discernable change in response to an exposure to the stimulus. The
operation 876 includes quantifying the exposure of the release
element of the chosen instance of the final dosage form to the
selected stimulus. The operation 876 may include at least one
additional operation. The at least one additional operation may
include an operation 878, or an operation 882. The operation 878
includes initiating another exposure of the release element of the
chosen instance of the final dosage form to the selected stimulus
in response to the quantifying the exposure of the release element
of the chosen instance of the final dosage form to the selected
stimulus. The operation 882 includes terminating the exposure of
the release element of the chosen instance of the final dosage form
to the selected stimulus in response to the quantifying the
exposure of the release element of the chosen instance of the final
dosage form to the selected stimulus.
[0162] FIG. 14 illustrates an embodiment of the example operational
flow 800 of FIG. 9. The operational flow 800 may include at least
one additional operation. The at least one additional operation may
include an operation 860, an operation 870, or an operation 890.
The operation 860 includes receiving the request specifying a dose
of a medicament for an individual animal. The operation 860 may
include at least one additional operation. The at least one
additional operation may include an operation 862, or an operation
864. The operation 862 (not shown) includes receiving the request
specifying an efficacious medicament dose for an individual animal.
The operation 864 (not shown) includes receiving the request
specifying the final dosage form that includes the medicament for
an individual animal.
[0163] The operation 870 includes verifying the exposure of the
release element of the chosen instance of the final dosage form to
the selected stimulus. The operation 890 includes dispensing the
chosen instance of the final dosage form after the exposure of the
release element of the chosen instance of the final dosage form to
the selected stimulus as described above. The operation 890 may
include at least one additional operation, such as an operation
892. The operation 892 (not shown) includes dispensing the ex vivo
exposed instance of the final dosage form in a package bearing an
identifier of the individual animal. For example, the identifier
may include a name, or identification number of the animal.
[0164] FIG. 15 illustrates an example environment 1000 that
includes the animal 198, a cross-sectional view of an example final
dosage form 1002 for administering the medicament 190 to the animal
198, and the example stimulus source 194 operable to emit a
stimulus 192. In an embodiment, the final dosage form includes a
dosage form having completed a manufacturing or production process.
In an embodiment, the final dosage form includes a product,
finished tablet, or capsule ready for distribution to a hospital,
pharmacy, or retail store for individualizing for a particular
animal. In an embodiment, the final dosage form includes a tablet
shape, a spherical shape, or an ellipsoidal shape. In an
embodiment, the final dosage form includes a structure, a particle,
or a polymer that is carryable or transportable to the animal by a
solid, cream, liquid, or fluid carrier.
[0165] The final dosage form 1002 includes an outer layer 1010, a
release element 1030, and the medicament 190. The release element
is configured in a medicament-holding state. The release element is
modifiable ex vivo to a medicament-discharge state by an exposure
to a stimulus, illustrated as the stimulus 192. In an embodiment,
ex vivo includes outside the body of the animal. In an embodiment,
ex vivo includes an environment outside or away from the body of
the animal. In an embodiment, ex vivo includes outside a living
organism, such as "in vitro." In an embodiment, ex vivo includes an
external or ambient environment.
[0166] In an embodiment, the stimulus 192 includes at least one of
a non-ionizing radiation, an electromagnetic radiation, a magnetic
field, an electric field, an energetic stimulus, or a chemical
stimulus. In an embodiment, the stimulus includes at least one of a
light radiation, terahertz radiation, microwave radiation, or radio
wave radiation. In an embodiment, the stimulus includes at least
one of a mechanically activatable structure, heat activatable
structure, or pressure activatable structure. In an embodiment, the
stimulus includes at least one of a thermal, acoustic, or
ultrasound stimulus. In an embodiment, the stimulus includes at
least one of an activation stimulus, or an actuation stimulus.
[0167] In an embodiment, the release element 1030 includes a
release element configured in a medicament-holding state. In the
medicament-holding state, the medicament 190 is substantially not
bioavailable to the animal 198 if the final dosage form 1002 is
administered to the animal. The release element is modifiable ex
vivo to a medicament-discharge state by an exposure to the stimulus
192. In the medicament-discharge state, the medicament is
substantially bioavailable to the animal if the final dosage form
is administered to the animal. In an embodiment, substantially not
bioavailable to the animal includes having no substantial
therapeutic or adverse effect on the animal. In an embodiment,
bioavailable to the animal includes the medicament being
physiologically available, absorbable, transportable, usable, or
utilizable by the animal. In an embodiment, bioavailable to the
animal indicates that a portion of an administered dose of
medicament reaches the systemic circulation. In an embodiment, not
bioavailable to the animal includes the medicament being
physiologically not available, not absorbable, not transportable,
not usable, or not utilizable by the animal.
[0168] In an embodiment, the release element 1030 includes a
release element configured in a medicament-holding state. In the
medicament-holding state, the medicament 190 is insubstantially
bioavailable if the final dosage form 1002 is administered to the
animal 198. The release element is modifiable ex vivo to a
medicament-discharge state by an exposure to the stimulus 192. In
the medicament-discharge state, the medicament is substantially
bioavailable if the final dosage form is administered to the
animal. In an embodiment, the release element includes a release
element configured in a medicament-holding state. In the
medicament-holding state, the medicament is substantially
bio-unavailable if the final dosage form is administered to the
animal. The release element is modifiable ex vivo to a
medicament-discharge state by an exposure to the stimulus wherein
the medicament is substantially bioavailable if the final dosage
form is administered to the animal. In an embodiment,
bio-unavailable includes present but not usable by the animal.
[0169] In an embodiment, the release element includes a release
element 1030 configured in a medicament-holding state. In the
medicament-holding state, the medicament 190 has a substantially
insignificant effect on the animal 198 if the final dosage form
1002 is administered to the animal. The release element is
modifiable ex vivo to a medicament-discharge state by an exposure
to the stimulus. In the medicament-discharge state, the medicament
has a substantially significant effect on the animal if the final
dosage form is administered to the animal. In an embodiment, the
release element includes a release element configured in a
medicament-withholding state, and modifiable ex vivo to a
medicament-supplying state by an exposure to the stimulus.
[0170] In an embodiment, the release element 1030 includes a
release element configured in a medicament-holding state and
field-modifiable ex vivo to a medicament-discharge state by an
exposure to the stimulus 192. For example, the release element may
be field modified at a point of administration of the final dosage
form, such as clinic or hospital, at a pharmacy such as when a
pharmacist is filling a prescription that includes the final dosage
form, or at a residence by a caregiver or by a person for whom the
final dosage form is prescribed. In an embodiment, the release
element includes a release element configured in a
medicament-holding state and modifiable ex vivo post-manufacture to
a medicament-discharge state by an exposure to the stimulus. In an
embodiment, the release element includes a release element forming
an imperforate barrier in a medicament-holding state. The release
element is modifiable ex vivo by an exposure to the stimulus to
form a perforate barrier in a medicament-discharge state. In an
alternative embodiment, the release element is modifiable ex vivo
by an exposure to the stimulus to form a perforate barrier in a
medicament-discharge state to form at least one discharge
pathway.
[0171] In an embodiment, the release element 1030 includes a
release element configured in a medicament-holding state. The
release element is modifiable ex vivo to a medicament-discharge
state by an exposure to the stimulus 192, the stimulus including at
least one of light or radio waves.
[0172] In an embodiment, the final dosage form 1002 includes a
particle or polymer implemented release element. In an embodiment,
a polymer may include an intelligent polymer having a changeable
property that in one state admits or discharges at least one
molecule of medicament and in another state engages or retains the
at least one molecule of medicament. An intelligent polymer
includes a polymer structurally responsive to an externally applied
energy or stimulus. In an embodiment, "applied energy" includes
both positive and negative energy values, i.e. supplying and
removing energy. Examples of intelligent polymers are described in
U.S. Pat. No. 7,104,517 to Derand, et al. In an embodiment, a
particle may include a microsphere, polymeric microsphere, or
nanoparticle.
[0173] FIG. 16 illustrates an example environment 1100 that
illustrates a final dosage form 1102 having a release element 1130
implemented by a characteristic response of a particle or a
polymeric material 1180 to a stimulus such as, the stimulus 192. An
example of the particle or polymeric material is illustrated as a
liposome. The final dosage form includes molecules of the
medicament 190 carried by the particle or a polymeric material,
again illustrated with respect to the liposome. Example
water-soluble drug molecules 190A are illustrated as engaged,
retained, or entrapped in an internal aqueous compartment site
1120A. Example lipid-soluble drug molecules 190B are illustrated as
engaged, retained or entrapped in a bilayer site 1120B. The example
environment 1100 illustrates the release element configured in a
medicament-holding state with at least one molecule of the
medicament engaged, retained or entrapped. In an embodiment, the
release element has, for example by application of a stimulus, such
as the stimulus 192, been changed into a state (not shown) that
admits at least one molecule of the medicament, illustrated as the
water-soluble drug molecules 190A or the lipid-soluble drug
molecules 190B. The release element state is changed by withdrawal
of the stimulus into a state (shown) that engages, retains or
entraps the water-soluble drug molecules 190A or the lipid-soluble
drug molecules 190B. Continuing this example, the release element
is modifiable ex vivo to a medicament-discharge state by an
exposure to a stimulus, such as the stimulus 192, which may be the
same stimulus used to switch the release element and load the
water-soluble drug molecules 190A or the lipid-soluble drug 190B
into the liposome, or may be another stimulus 192. In an
alternative of this example, a chemical stimulus may be used to
load the at least one molecule in the liposome, and another
stimulus, such as an electromagnetic wave used to modify the
liposome to a medicament-discharge state.
[0174] The characteristic response of the particle or polymeric
material to the stimulus 192 may include any characteristic
response that releases an engaged, retained, or entrapped
medicament 190 from the particle or polymeric material. For
example, a characteristic response of a particular particle or
polymeric material may include a releasing bursting, expanding,
cleaving, or degradation of the particular particle or polymeric
material in response to a microwave stimulus implements the release
element 1130.
[0175] In an embodiment, the release element 1130 is configured in
a medicament-holding state. The release element is modifiable ex
vivo to a medicament-discharge state by an exposure to the stimulus
192. The release element including at least one of a gel, gel
matrix, hydrogel fibrin, or a dendrimer. Examples hydrogels are
described in Y. Qiu, et al, Enivoronment-sensitive hydrogels for
drug delivery, SCIENCEDIRECT (October 2001), citing Triggering in
Drug Delivery Systems, 53 ADVANCED DRUG DELIVERY REVIEWS 321-339
(Issue 3, December 2001). Examples polymers and dendrimers are
described in C. Henry, Drug Delivery, 80 CHEMICAL & ENGINEERING
NEWS 39-47 (No. 34, Aug. 26, 2002) (The drugs are conjugated to the
dendrimers using photocleavable or labile linkers, which can be
made to release the drug using light or through acid cleavage).
Examples of photo-labile, radio-labile, and enzyme-labile
dendrimers are described in U.S. Pat. No. 6,471,968 to Baker, et
al.; and in U.S. Pat. No. 7,078,461 to Tomalia, et al. In an
embodiment, a particle or polymeric material having a
characteristic responsive to an exposure to the stimulus include an
intelligent or environmentally sensitive particle or polymeric
material.
[0176] In an embodiment, the release element 1130 includes a
particle (not specifically shown) configured in a
medicament-holding state. The particle is modifiable ex vivo to a
medicament-discharge state by an exposure to the stimulus 192.
Examples of environmentally sensitive particles such as
microspheres have been described previously herein. In an
embodiment, the release element includes a polymer substance
configured in a medicament-holding state. The polymer substance is
modifiable ex vivo to a medicament-discharge state by an exposure
to the stimulus. Examples of environmentally sensitive polymer
substances have been described previously herein.
[0177] Returning to FIG. 15, in an embodiment, the release element
1030 includes a non-shape-memory material configured in a
medicament-holding state. The non-shape-memory material is
modifiable ex vivo to a medicament-discharge state by an exposure
to the stimulus 192. In an embodiment, the release element includes
a release element disposed at least partially within the outer
layer 1010 and configured in a medicament-holding state. The
release element is modifiable ex vivo to a medicament-discharge
state by an exposure to the stimulus. In the medicament-discharge
state the medicament 190 is substantially available for an in vivo
release into the animal 198 if the final dosage form is
administered to the animal while the release element is configured
in the medicament-discharge state.
[0178] In an embodiment, the final dosage form 1002 further
includes a chamber 1020 located substantially within the outer
layer 1010 and carrying the medicament 190. In an embodiment, the
chamber 1020 is substantially similar to the chamber 120 described
in conjunction with FIG. 1. In an embodiment, the final dosage form
further includes the indicator element 180 configured to indicate
an exposure of the release element 1030 to the stimulus 192.
[0179] Another embodiment provides a final dosage form 1002 for
administering the medicament 190 to the animal 198. This embodiment
of the final dosage may be illustrated by reference to FIG. 15
and/or by reference to FIG. 16. With reference to an embodiment
illustrated by FIG. 15, the final dosage form 1002 includes a
release element 1030, a site 1020 carrying the medicament, the
medicament, and a containment element 1040. The release element
1030 is configured in a medicament-holding state and modifiable ex
vivo to a medicament-discharge state by an exposure to the stimulus
192. The containment element retains the medicament within the
final dosage form until the final dosage form is administered to
the animal. In an embodiment, the containment element may be
substantially similar to the containment element 140 described in
conjunction with FIG. 1.
[0180] With reference to an embodiment illustrated by FIG. 16, an
embodiment of the final dosage form includes the final dosage form
1102 having a release element 1130 formed by a particle or polymer
1180, a site carrying the medicament 190 (depicted as the internal
aqueous compartment site 1120A or as the bilayer site 1120B), the
medicament. The release element is configured in a
medicament-holding state and modifiable ex vivo to a
medicament-discharge state by an exposure to the stimulus.
[0181] In an embodiment, the final dosage form 1102 includes a
containment element 1140. The containment element retains the
medicament within the final dosage form until the final dosage form
is administered to the animal. In an embodiment, the containment
element 1140 includes a particle or polymeric substance retaining
the medicament 190 within the final dosage form 1102 until the
final dosage form is administered to the animal 198 (not shown).
For example, the containment element may include a gel, hydrogel,
liposome microsphere, polymeric microsphere, dendrimer, or
nanoparticle. In an embodiment, the containment element may be
another particle or polymer that engages, retains, or entraps the
particle or polymer in a containing manner (not shown). In an
embodiment, the containment element may be substantially similar to
the containment element 140 of the final dosage from 102 described
in conjunction with FIG. 1. In an embodiment, the containment
element may be substantially similar to the erodible outer layer
110 of the final dosage form 102 described in conjunction with FIG.
1. In an embodiment, the release element 1130 and the containment
element are at least a substantially same structure, for example a
microsphere. In an embodiment, the release element and the
containment element are substantially different structures, for
example a microsphere containment element containing a dendrimer
release element. In an embodiment, the containment element includes
a carrier, excipient, diluent, or admixture retaining the
medicament within the final dosage form until the final dosage form
is administered to the animal.
[0182] In an embodiment, the site 1120 carrying the medicament 190
includes a chamber carrying the medicament. In an embodiment, the
site carrying the medicament includes a region carrying the
medicament. In an embodiment, the site carrying the medicament
includes a binding site releasably carrying the medicament. In an
embodiment, the site carrying the medicament includes the release
element 1130 or a particle or polymeric material carrying the
medicament. In an embodiment, the site carrying the medicament
includes a binding site releasably carrying the medicament.
[0183] In an embodiment, the final dosage form includes an
indicator element 180 configured to indicate an exposure of the
release element to the stimulus. With reference to an embodiment
illustrated by FIG. 15, the final dosage form 1002 includes an
indicator element 180 configured to indicate an exposure of the
release element 1030 to the stimulus 192. With reference to FIG.
16, the final dosage form 1102 includes an indicator element (not
shown) configured to indicate an exposure of the release element
1130 to the stimulus 192.
[0184] FIG. 17 illustrates an example environment 1200 that
includes an article 1201. The article includes at least one final
dosage form for administering a therapeutically effective amount of
a medicament to an animal. In an embodiment, the final dosage form
includes a final dosage 1202 that is substantially similar to the
final dosage form 1002 described in conjunction with FIG. 15. In an
embodiment, the final dosage form includes the final dosage form
1202 that is substantially similar to the final dosage form 1102
described in conjunction with FIG. 16 (not shown in FIG. 17). The
final dosage form of FIG. 17 includes an outer layer 1210, a
release element 1230, a site 1220 carrying the medicament 190. The
release element includes a release element configured in a
medicament-holding state. The release element is modifiable ex vivo
to a medicament-discharge state by an exposure to the stimulus 192.
The article also includes instructions 1270 for the exposure of the
release element to the stimulus sufficient to modify the release
element to the medicament-discharge state. In an embodiment, the
instructions include instructions specifying the exposure of the
release element to a human-initiated stimulus sufficient to modify
the release element to the medicament-discharge state. In an
embodiment, the instructions include instructions specifying the
exposure of the release element to provide an
automatically-initiated stimulus sufficient to modify the release
element to the medicament-discharge state.
[0185] FIG. 18 illustrates an example operational flow 1300
modifying a medicament availability characteristic of a final
dosage form. A start operation occurs in an environment 1305 that
includes the final dosage form. The final dosage form includes an
outer layer, a release element, a site carrying the medicament, and
the medicament. The release element is configured in a
medicament-holding state wherein a medicament is substantially not
bioavailable to the animal, such as the animal 198. The release
element is modifiable ex vivo to a medicament-discharge state by an
exposure to the stimulus wherein the medicament is substantially
bioavailable to the animal. In an embodiment, the final dosage form
is substantially similar to the final dosage form 1002 described in
conjunction with FIG. 15. In an embodiment, the final dosage form
is substantially similar to the final dosage form 1102 described in
conjunction with FIG. 16
[0186] After the start operation, the operational flow 1300
includes an activating operation 1310. The activating operation
includes initiating an exposure of a release element of the final
dosage form to a stimulus, such as the stimulus 192. The initiated
stimulus is selected to transform the release element from a
medicament-holding state to a medicament-discharge state. In an
embodiment, the initiated stimulus includes an initiated stimulus
having a parameter selected to transform the release element from a
medicament-holding state to a medicament-discharge state. In an
embodiment, the initiated stimulus includes an initiated stimulus
having at least one of a stimulation characteristic or a spatial
characteristic selected to transform the release element from a
medicament-holding state to a medicament-discharge state. In an
embodiment, the initiating an exposure of a release element of the
final dosage form to a stimulus includes initiating a first
exposure of a release element of the final dosage form to a
stimulus. The initiated first stimulus is selected to transform the
release element from a medicament-holding state to a
medicament-discharge state. This embodiment further includes
receiving an indication of the first exposure of the release
element of the final dosage form to the stimulus, the indication
generated in response to an indicator element of the final dosage
form configured to indicate an exposure of the release element to
the stimulus. This embodiment further includes initiating a second
exposure of the release element of the final dosage form to the
stimulus. The initiated second exposure stimulus is selected to
further transform the release element from the medicament-holding
state to the medicament-discharge state.
[0187] In an embodiment, the final dosage form includes a
containment element retaining the medicament within the final
dosage form until the final dosage form is introduced into the
animal. In an embodiment, the final dosage form includes an
indicator element configured to indicate an exposure of the release
element to the stimulus.
[0188] FIG. 19 illustrates an example final dosage form 1400 for
administering a medicament to an animal. The final dosage includes
means 1410 for protecting the final dosage form from an ex vivo
environment. The final dosage form includes means 1420 for
releasing the medicament, configured in a medicament-holding state,
and modifiable ex vivo to a medicament-discharge state by an
exposure to a stimulus, such as the stimulus 192. The final dosage
form includes the medicament 1430.
[0189] In an embodiment, the final dosage form includes means 1440
for carrying the medicament. In an embodiment, the means 1440 for
carrying the medicament is positioned substantially within the
means 1410 for protecting the final dosage form. In an embodiment,
the final dosage form includes means 1450 for indicating an
exposure of the means for releasing the medicament to the stimulus.
In an embodiment, the final dosage form includes means 1460 for
containing the medicament within the final dosage form until the
final dosage form is introduced into the animal.
[0190] An embodiment provides a final dosage form for administering
a medicament to an animal. In this embodiment, the final dosage
form includes at least one particle or polymeric material
respectively carrying at least one molecule of the medicament. The
particle or polymeric material is configured in a
medicament-retention state wherein the medicament is substantially
not bioavailable to the animal if the final dosage form is
administered to the animal. The particle or polymeric material is
modifiable ex vivo by an exposure to the stimulus to a
medicament-release state wherein the medicament is substantially
bioavailable to the animal if the final dosage form is administered
to the animal. This embodiment is described, for example, by
reference to FIG. 16, FIG. 20, and/or FIG. 21. In an embodiment,
the particle or polymeric material may include at least one of the
particle or polymeric materials previously described. In an
embodiment, the particle or polymeric material includes an
intelligent particle or polymeric material. In an embodiment, the
particle or polymeric material includes a polymer matrix structure
responsive to the exposure to a stimulus. In an embodiment, the
particle or polymeric material includes at least one of a
microparticle, a gel or a dendrimer based microparticle responsive
to the exposure to a stimulus. In an embodiment, the particle or
polymeric material includes at least one of a noisome, fibrin,
polymeric micelle, microsome, cyclodextrin, polymer-medicament
conjugate, or cellulose responsive to the exposure to a stimulus.
In an embodiment, the particle or polymeric material includes at
least one of a gel, a gel matrix, a natural gel, a synthetic gel, a
colloid gel, or a hydrogel structure covalently bonded to the
medicament using a photo labile bond and responsive to the exposure
to a stimulus. A synthetic gel may include cellulose or polymers.
In an embodiment, the particle or polymeric material includes at
least one of a dendrimer, dendrimsome, dendromsome, dendron
(partial dendrimer), or dendriplex material. In an embodiment, the
particle or polymeric material includes at least one of an
emulsion, nano-emulsion, or double emulsion. In an embodiment, the
particle or polymeric material includes at least one of a lipid,
cationic lipid, lipid micelle, liposome, lipospheres, acoustically
active lipospheres, acoustically-active microbubbles conjugated to
liposomes, lipid-coated microbubbles, cerasomes, magnetic
liposomes, metallosomes, or a mimetic. Acoustically-active
microbubbles conjugated to liposomes are described in A.
Kheirolomoom, et al., Acoustically-active microbubbles conjugated
to liposomes: characterization of a proposed drug delivery vehicle,
J. CONTROL RELEASE 118(3) (Apr. 23, 2007):275-84; Epub 2006 Dec.
23. A cerasomes may include liposomes with a silicate surface. A
mimetic may include an artificial micelle or membrane.
[0191] FIG. 20 illustrates an example environment 1500 that
includes a final dosage form 1502 configurable to administer a
medicament to the animal 198. The final dosage form includes at
least one molecule of the medicament 190. The final dosage form
also includes at least one of a particle or polymeric material
1580, which is depicted as a gel. The particle or polymeric
material has a characteristic response 1530 to the stimulus 192
that releases an engaged, retained, or entrapped at least one
molecule of the medicament 190 from the particle or polymeric
material. For example, a characteristic response of a particular
particle or polymeric material may include a releasing bursting,
expanding, cleaving, or degradation of the particular particle or
polymeric material in response to a microwave stimulus.
[0192] The at least one particle or polymeric material 1580
respectively carries the at least one molecule of the medicament
190. The particle or polymeric material is configured in a
medicament-retention state wherein the medicament is substantially
not bioavailable to the animal 198 if the final dosage form is
administered to the animal. The particle or polymeric material
being modifiable ex vivo by an exposure to the stimulus 192 to
carry the medicament in a medicament-release state wherein the
medicament is substantially bioavailable to the animal if the final
dosage form is administered to the animal.
[0193] FIG. 21 illustrates an example environment 1600 depicting
retention and release states of particle or polymeric material 1680
(depicted as a hydrogel) carrying the medicament 190 and responsive
to an ex vivo stimulus 192. FIG. 21A illustrates a
medicament-release state where two instances of the medicament,
collectively labeled "190 Released," have been released from the
particle or polymeric material in a medicament-release state. FIG.
21B illustrates a medicament-retention state where two instances of
the medicament, collectively labeled "190 Retained" are carried by
the particle or polymeric material in a medicament-retention state.
Application of the stimulus ex vivo to the particle or polymeric
material switches it from the medicament-retention state to the
medicament-release state. For example, an ex vivo application of
the stimulus to the hydrogel switches it from a pore "closed" state
1630-C to a pore "open" state 1630-O.
[0194] Returning to FIG. 16, FIG. 16 illustrates the particle or
polymeric material 1180, which is depicted as a liposome. The
particle or polymeric material carries the medicament 190. The
particle or polymeric material is configured in a
medicament-retention state wherein the medicament is substantially
not bioavailable to the animal if the final dosage form is
administered to the animal 198. The particle or polymeric material
is modifiable ex vivo by an exposure to the stimulus 192 to carry
the medicament in a medicament-release state wherein the medicament
is substantially bioavailable to the animal if the final dosage
form is administered to the animal.
[0195] Returning to FIG. 20, in an embodiment, the medicament 190
includes a pharmacologically-active agent. In an embodiment, the
medicament includes at least one of an agent, treatment agent,
drug, prodrug, therapeutic, nutraceutical, medication, vitamin,
nutritional supplement, medicine, remedy, medicinal substance, or
cosmetic.
[0196] In an embodiment, the particle or polymeric material 1580
carrying the medicament 190 includes a particle or polymeric
material conjugated with the medicament. In an embodiment, the
particle or polymeric material carrying the medicament includes a
particle or polymeric material containing, intertwined, or bound
with the medicament. In an embodiment, the particle or polymeric
material carrying the medicament includes a particle or polymeric
material entrapping the medicament.
[0197] In an embodiment, the particle or polymeric material 1180
carrying the medicament 190 includes a particle or polymeric
material carrying the medicament 190 and configured in a
medicament-withholding state. In the medicament-withholding state
the medicament is substantially not bioavailable to the animal 198
if the final dosage form 1102 is administered to the animal 198.
The particle or polymeric material is modifiable ex vivo by an
exposure to the stimulus 192 to carry the medicament in a
medicament-supplying state wherein the medicament is substantially
bioavailable to the animal if the final dosage form is administered
to the animal. In an embodiment, the particle or polymeric material
includes a particle or polymeric material carrying the medicament
and configured in a medicament-retention state. In the
medicament-retention state the medicament is substantially not
bioavailable to the animal if the final dosage form is administered
to the animal. The particle or polymeric material is modifiable ex
vivo upon at least one of a post-manufacture or a field exposure to
the stimulus to a medicament-release state. In medicament-release
state, the medicament is substantially bioavailable to the animal
if the final dosage form is administered to the animal. In an
embodiment, the particle or polymeric material includes a particle
or polymeric material carrying the medicament and configured in a
medicament-holding state. In the medicament-holding state the
medicament is substantially not bioavailable to the animal if the
final dosage form is administered to the animal. The particle or
polymer material is modifiable ex vivo to an in vivo
release-facilitation state by an exposure to the stimulus to a
medicament-release state. In the in vivo release-facilitation state
the medicament is substantially bioavailable to the animal if the
final dosage form is administered to the animal.
[0198] In an embodiment, the particle or polymeric material 1580
includes a particle or polymeric material having a premodification
characteristic that results in an insignificant uptake of the
particle or polymeric material in the gastrointestinal tract of the
animal 198. In an embodiment, the particle or polymeric material
includes an intact particle or polymeric material having a
premodification characteristic that results in an insignificant
uptake of the particle or polymeric material in the
gastrointestinal tract of the animal. In an embodiment, the
particle or polymeric material includes at least one of a gel, gel
matrix, or hydrogel structure covalently bonded to the medicament
using a photo labile bond. An example of a medicament covalently
bonded to a hydrogel using photo labile bonds, and the medicament
is not be released unless the gel matrix is exposed to enough light
to break the bonds is described in U.S. Pat. No. 6,985,770 to
Nyhart, Jr. An example of a medicament conjugated to dendrimers
using photocleavable or labile linkers, which can be made to
release the drug using light or through acid cleavage is described
in Y. Qiu, supra., and C. Henry, supra. In an embodiment, the
particle or polymeric material includes at least one of a
dendrimer, dendrimsome, or dendriplex material. Examples of
photo-labile, radio-labile, and enzyme-labile dendrimers are
described in U.S. Pat. No. 6,471,968 to Baker, et al.; and examples
of photo labile biocompatible dendrimers made from
poly(propyleneimine) (POPAM) interiors and poly(amidoamine) (PAMAM)
are described in U.S. Pat. No. 7,078,461 to Tomalia, et al.
[0199] In an embodiment, the particle or polymeric material 1580
includes a liposome carrier entrapping the medicament and having an
intact particle size resulting in an insignificant uptake in the
gastrointestinal tract of the animal 198. In an embodiment, the
particle or polymeric material includes a liposome carrier having a
particle size of at least approximately three microns. An example
of a liposome carrier having a particle size of at least
approximately three microns resulting an insignificant uptake in
the gastrointestinal tract of the animal is described in D.
Deshmukh, Can intact liposomes be absorbed in the gut? LIFE SCI.
1981 Jan. 19; 28(3):239-42; See also, MARC J. OSTRO, LIPOSOMES:
FROM BIOPHYSICS TO THERAPEUTICS 140 (1987); 42 J. PHARMACY AND
PHARMACOLOGY 821-826 (1990); 86 INTER. J. PHARMACY 239-246 (1992);
PHARMACEUTICAL PARTICULATE CARRIERS: THERAPEUTIC APPLICATIONS Ch. 4
(p. 65, and FIGS. 15 and 16 at page 92) (edited By Alain Rolland
1993). In an embodiment, the particle or polymeric material
includes a liposome having a particle size of at least
approximately four microns.
[0200] In an embodiment, the particle or polymeric material 1580
includes at least one of a nanoparticle, a microsphere, or a
polymeric microsphere responsive to the exposure to the stimulus
192. In an embodiment, the particle or polymeric material includes
a pharmaceutically-acceptable inert particle or polymeric
material.
[0201] In an embodiment, the stimulus 192 includes a non-ionizing
radiation stimulus. In an embodiment, the stimulus includes an
electromagnetic radiation stimulus. In an embodiment, the stimulus
includes at least one of a light radiation, terahertz radiation,
microwave radiation, and radio wave radiation stimulus. In an
embodiment, the stimulus includes a magnetic stimulus. In an
embodiment, the stimulus includes an electric stimulus. In an
embodiment, the stimulus includes an energetic stimulus. In an
embodiment, the stimulus includes a chemical stimulus. In an
embodiment, the stimulus includes at least one of a mechanical,
heat, or pressure stimulus. In an embodiment, the stimulus includes
at least one of an activation stimulus, or an actuation stimulus.
In an embodiment, the stimulus includes at least one of at least
one of a thermal, acoustic, or ultrasound stimulus. In an
embodiment, the stimulus includes a stimulus facilitating a release
of the medicament by at least one of an expansion of a gel, gel
matrix, or hydrogel carrier. In an embodiment, the stimulus
includes a stimulus facilitating a release of the medicament by at
least one of an expansion of a gel, gel matrix, or hydrogel carrier
to allow a diffusion and bioavailability of the medicament. In an
embodiment, the stimulus includes a stimulus facilitating the
release of the medicament from the particle or polymeric carrier by
at least one of a bursting of a liposome material, formation of a
pore in a liposome material, or an unpacking of the particle or
polymeric material.
[0202] In an embodiment, the particle or polymeric material 1580
includes a particle or polymeric material carrying the medicament
190 and configured in a medicament-retention state wherein the
medicament is substantially not bioavailable to the animal 198 if
the final dosage form is administered to the animal. The particle
or polymeric material modifiable ex vivo by an exposure to the
stimulus 192 to carry the medicament in a medicament-release state
allowing an in vivo release of the medicament if the final dosage
form is administered to the animal.
[0203] In an embodiment, the particle or polymeric material 1580
includes a first particle or polymeric material carrying the
medicament 190, and a second particle or polymeric material (not
shown) carrying the first particle or polymeric material. The
second particle or polymeric material is configured in a first
particle or polymeric material-retention state wherein the first
particle or polymeric material is substantially not bioavailable to
the animal if the final dosage form is administered to the animal
198. The second particle or polymeric material is modifiable ex
vivo by an exposure to the stimulus 192 to carry the medicament a
first particle or polymeric material-release state wherein the
first particle or polymeric material is substantially bioavailable
to the animal if the final dosage form is administered to the
animal.
[0204] In an embodiment, the final dosage form 1502 further
includes a transport medium 1560 suitable for administering the
particle or polymeric material 1580 carrying the medicament to the
animal 198. For example, the transport medium may include a
carrier, admixture, diluent, or excipient. In another example, the
transport medium may include a polymer, such as a hydrogel. An
example of a polymer transport medium is described in United States
Patent Application Pub. 2008/0050445 by Alcantar. In an embodiment,
the final dosage form further includes an indicator substance (not
illustrated) configured to indicate an exposure of the particle or
polymeric substance to the stimulus 192. In an embodiment, the
final dosage form further includes an indicator substance (not
illustrated) configured to visually indicate an exposure of the
particle or polymeric substance to the stimulus 192.
[0205] An embodiment includes the final dosage form for
administering the medicament 190 to the animal 198. In this
embodiment, the final dosage form includes the medicament and a
particle or polymeric material. The particle or polymeric material
carries the medicament. The particle or polymeric material is
configured in a medicament-retention state wherein the medicament
is substantially not bioavailable to the animal if the final dosage
form is administered to the animal. The particle or polymeric
material is modifiable ex vivo by an exposure to a first stimulus
to carry the medicament a first medicament-release state wherein
the medicament has a first bioavailability to the animal if the
final dosage form is administered to the animal. The particle or
polymeric material is modifiable ex vivo by an exposure to a second
stimulus to carry the medicament in a second medicament-release
state wherein the medicament has a second bioavailability to the
animal if the final dosage form is administered to the animal.
Understanding of this embodiment may be facilitated by reference to
the preceding description in conjunction with FIG. 16, FIG. 20, or
FIG. 21.
[0206] In an embodiment, the first bioavailability includes a first
delivery rate of the medicament and the second bioavailability
includes a second delivery rate of the medicament. For example, the
particle or polymeric material may have a characteristic that
include an adjustable pore size responsive to a temperature of the
particle or polymeric material attained in response to a heat
stimulus. The heat stimulus may include a microwave or a light
source. The first stimulus may include an exposure of the particle
or polymeric material to a first temperature, or to a given
temperature for a first period of time. The second stimulus may
include an exposure of the particle or polymeric material to a
second temperature, or to a given temperature for a second period
of time. For example, selective control of temperature-modulatable
materials is described in G. Rao, et al., Synthesis of Smart
Mesoporous Materials, MRS BULLETIN P7.8 (Spring 2003). For example,
an adjustable porosity of an organic polymer membrane is described
in R. Estrada, et al., Smart polymeric membranes with adjustable
pore size, 52 International journal of polymeric materials 833-843
(No. 9, 2003). For example, a thermosensitive grafted polymeric
system which can be triggered to release the loaded drug with an
increase in temperature, induced by a magnetic thermal heating
event, is described in I. Ankareddi, et al., Development of a
Magnetically Triggered Drug Delivery System using Thermoresponsive
Grafted Polymer Networks with Magnetic Nanoparticles, 2 NANOTECH
431-434 (Vol. 2, 2007). See also, R. Liburdy, et al.,
Microwave-triggered liposomal drug delivery: investigation of a
model drug delivery system, Engineering in Medicine and Biology
Society 1163-1164, (Vol. 4, November 1989) (Images of the
Twenty-First Century, Proceedings of the Annual International
Conference of the IEEE Engineering). In another example, the first
stimulus may include a first ultrasound power density and the
second stimulus may include a second ultrasound power density. For
example, bioavailability of polymeric micelles as a variable
function of ultrasound power density is at least suggested by A.
Marin, et al., Acoustic activation of drug delivery from polymeric
micelles: effect of pulsed ultrasound, 71 JOURNAL OF CONTROLLED
RELEASE 239-249 (Issue 3, 28 Apr. 2001).
[0207] In an embodiment, the final dosage form 1502 configurable to
administer a medicament to the animal 198 includes a containment
element 1540. In an embodiment, the containment element 1540 may be
substantially similar to the containment element 140 described in
conjunction with FIG. 1. In an embodiment, the containment element
1540 includes a pH-sensitive component of a liposome. For example,
S. Cho, et al, pH-dependent release property of
dioleoylphosphatidyl ethanolamine liposomes, 25 KOREAN JOURNAL OF
CHEMICAL ENGINEERING 390 (No. 2, 2008) describes a pH-sensitive
liposome prepared by a detergent removal method that retains at
neutral pH (6-8), and releases at pH 5. In an embodiment, the
containment element includes tunable component of a liposome. For
example, I. Hafez, et al., Tunable pH-Sensitive Liposomes Composed
of Mixtures of Cationic and Anionic Lipids, 79 BIOPHYSICAL JOURNAL
1438 (Issue 3, 2000) describes a tunable liposome using cationic
and anionic lipid mixtures (cholesteryl hemisuccinate (CHEMS) and
N,N-dioleoyl-N,N-dimethylammonium chloride. In an embodiment, the
containment element includes pH sensitive Chitosan and
polyacrylamide copolymer hydrogels releasing contained substances
upon pH changes. For example, as described in P. Bonina, et al., 19
JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS 101 (No. 2, 2004). In
an embodiment, the containment element includes a pH sensitive
Chitosan and polyalkyleneoxide-maleic acid copolymer releasing
substances on pH changes. For example, as described in T.
Yoshizawa, et al., pH-and temperature-sensitive permeation through
polyelectrolyte complex films composed of chitosan and
polyalkyleneoxide-maleic acid copolymer, 241 JOURNAL OF MEMBRANE
SCIENCE 347 (Issue 2, 2004). In an embodiment, the containment
element includes an acrylic acid (AA) grafted onto porous
polypropylene (PP) producing a pH sensitive membrane. For example,
as described in Y. Wang, et al., pH sensitive polypropylene porous
membrane prepared by grafting acrylic acid in supercritical carbon
dioxide, 45 POLYMER 855 (No. 3, 2004).
[0208] FIG. 22 illustrates an example environment 1700 that
includes an article of manufacture 1701. The article of manufacture
includes at least one final dosage form 1702 for administering the
medicament 190 to the animal 198. The final dosage form includes
the medicament, a particle or polymeric material 1780 carrying the
medicament, and an instruction 1770. In an embodiment, the particle
or polymeric material carrying the medicament may include the
particle or polymeric material described in conjunction with FIG.
20. In an embodiment, the particle or polymeric material carrying
the medicament may include a particle or polymeric material
described in this paper. An embodiment of the particle or polymeric
material carrying the medicament is depicted in FIG. 22 as a gel
material for illustrative purposes. The particle or polymeric
material has a characteristic response 1730 to the stimulus 192
that releases an engaged, retained, or entrapped at least one
molecule of the medicament 190 from the particle or polymeric
material. For example, a characteristic response of a particular
particle or microparticle may include a releasing bursting,
expanding, cleaving, or degradation of the particular particle or
microparticle in response to a microwave stimulus.
[0209] The particle or polymeric material 1780 is in a
medicament-retention state wherein the medicament is substantially
not bioavailable to the animal 198 after administration of the
final dosage form. The particle or polymeric material is modifiable
ex vivo to a medicament-release state by an exposure to the
stimulus 192 wherein the medicament is substantially bioavailable
to the animal after administration of the final dosage form.
[0210] The instruction 1770 includes an instruction for the
exposure of the particle or polymeric material 1780 to a
human-initiated stimulus 192 sufficient to transform the particle
or polymeric material to allow a discharge of at least a portion of
the therapeutically effective amount of the medicament from the
particle or polymeric carrier.
[0211] In an embodiment, the article of manufacture 1701 further
includes a label associated with the at least one final dosage form
1702 or an insert into a package 1760 containing the at least one
final dosage form, the insert providing the instructions 1770. In
an embodiment, the final dosage form further includes a transport
medium 1765 suitable for administering the particle or polymeric
material 1780 carrying the medicament 190 to the animal 195. In an
embodiment, the final dosage form further includes an indicator
substance (not shown) configured to indicate an exposure of the
particle or polymeric material to the stimulus 192.
[0212] FIG. 23 illustrates an example environment 1800 that
includes a final dosage form 1802 for administering the medicament
190 to the animal 198. The final dosage form includes at least one
molecule of the medicament and a particle or polymeric carrier
1880, is depicted as a gel, and which is operable to bind the at
least one molecule of the medicament. The particle or polymeric
carrier is configured in a first medicament-bioavailability state,
and modifiable ex vivo to a second medicament-bioavailability state
by an exposure to a stimulus, illustrated as the stimulus 192. In
an embodiment, the particle or polymeric carrier operable to bind
the at least one molecule of the medicament has a characteristic
response 1830 to a stimulus, such as the stimulus 192, that
releases the bound at least one molecule of the medicament 190 from
the particle or polymeric carrier. An example of such
characteristic response is described in conjunction with FIG. 21.
In another embodiment, the particle or polymeric carrier operable
to bind the at least one molecule of the medicament has a
characteristic response 1830 to a stimulus, such as the stimulus
192, that unbinds or releases the at least one molecule of the
medicament 190 from the particle or polymeric carrier.
[0213] In an embodiment, the particle or polymeric carrier 1880
includes a pharmaceutically-acceptable inert particle or polymeric
carrier operable to bind the at least one molecule of the
medicament 190. In an embodiment, the particle or polymeric carrier
includes a particle or polymeric carrier operable to engage,
retain, or entrap at least one molecule of the medicament.
[0214] In an embodiment, the first medicament-bioavailability state
is configured to retard medicament release in vivo and the second
medicament-bioavailability state is configured to allow medicament
release in vivo. In an embodiment, the first
medicament-bioavailability state is configured to allow medicament
release in vivo and the second medicament-bioavailability state is
configured to retard medicament release in vivo.
[0215] In an embodiment, the particle or polymeric carrier 1860
includes a liposome carrier operable to bind the at least one
molecule of the medicament 190 and having an intact particle size
resulting in an insignificant uptake in the gastrointestinal tract
of the animal 198. In an embodiment, liposome carrier operable to
bind the at least one molecule of the medicament and having an
intact particle size resulting in an insignificant uptake in the
gastrointestinal tract of the animal includes a liposome carrier
operable to bind the at least one molecule of the medicament and
having an intact particle size of at least approximately one
micron. For a description of an example, see, P. Hoet, et al.,
Nanoparticles--known and unknown health risks, 2 JOURNAL OF
NANOBIOTECHNOLOGY 12, at section 4 (2004). In an embodiment, the
liposome carrier operable to bind the at least one molecule of the
medicament and having an intact particle size resulting in an
insignificant uptake in the gastrointestinal tract of the animal
includes a liposome carrier operable to bind the at least one
molecule of the medicament and having an intact particle size of at
least approximately three microns. In an embodiment, the liposome
carrier operable to bind the at least one molecule of the
medicament and having an intact particle size resulting in an
insignificant uptake in the gastrointestinal tract of the animal
includes a liposome carrier operable to bind the at least one
molecule of the medicament and having an intact particle size of at
least approximately four microns.
[0216] In an embodiment, the final dosage form 1802 further
includes a transport medium 1860 suitable for administering to the
animal 198 the particle or polymeric carrier 1880 holding the at
least one molecule of the medicament 190. In an embodiment, the
final dosage form of claim further includes an indicator substance
(not shown) configured to visually indicate an exposure of the
particle or polymeric carrier holding the at least one molecule of
the medicament to the stimulus 192.
[0217] In an embodiment, the final dosage form 1802 configurable to
administer a medicament 190 to the animal 198 includes a
containment element 1840. In an embodiment, the containment element
1840 may be substantially similar to the containment element 140
described in conjunction with FIG. 1. In an embodiment, the
containment element 1840 may be substantially similar to the
containment element 1540 described in conjunction with FIG. 20.
[0218] FIG. 24 illustrates an example environment 1900 that
includes a final dosage form 1905 and an operational flow 1910. The
final dosage form includes the medicament and a particle or
polymeric material. The particle or polymeric material carries the
medicament in the medicament-retention state wherein the medicament
is substantially not bioavailable if the final dosage form is
administered to the animal, such as the animal 198. The particle or
polymeric material is transformable to the medicament-release state
by the exposure to a stimulus, such as the stimulus 192, wherein
the medicament is substantially bioavailable if the final dosage
form is administered to the animal. In an embodiment, the final
dosage form is at least similar to the final dosage form 1102
described in conjunction with FIG. 16. In an embodiment, the final
dosage form is at least similar to the final dosage form 1502
described in conjunction with FIG. 20. In an embodiment, the final
dosage form may is least similar to the final dosage form 1802
described in conjunction with FIG. 23. After a start operation, the
operational flow includes an activation operation 1920. The
activation operation includes initiating an exposure of the
particle or polymeric material of the final dosage form to a
stimulus, such as the stimulus 192 previously described. The
initiated stimulus is selected to transform the particle or
polymeric material from the medicament-retention state to the
medicament-release state.
[0219] In an embodiment, the final dosage form 1905 further
includes a containment element retaining the medicament within the
final dosage form until the final dosage form is introduced into
the animal. In an embodiment, the final dosage form further
includes an indicator element configured to indicate an exposure of
the particle or polymeric material to the stimulus.
[0220] FIG. 25 illustrates alternative embodiments of the
activation operation 1920 of FIG. 24. The activation operation may
include an operation 1922, an operation 1924, or an operation 1926.
The operation 1922 includes an initiated stimulus having a
parameter selected to transform the particle or polymeric material
from a medicament-retention state to a medicament-release state.
The operation 1924 includes an initiated stimulus having at least
one of a stimulation characteristic or a spatial characteristic
selected to transform the particle or polymeric material from a
medicament-retention state to a medicament-release state. The
operation 1926 includes initiating a first exposure of a particle
or polymeric material of the final dosage form to a stimulus, the
first initiated stimulus selected to transform the particle or
polymeric material from a medicament-retention state to a
medicament-release state. The operation 1926 also includes
receiving an indication of the first exposure of the release
element of the final dosage form to the stimulus, the indication
generated in response to an indicator element of the final dosage
form configured to indicate an exposure of the release element to
the stimulus. The operation 1926 further includes initiating a
second exposure of the release element of the final dosage form to
the stimulus, the initiated second exposure stimulus selected to
further transform the release element from the medicament-holding
state to the medicament-discharge state.
[0221] FIG. 26 illustrates an example embodiment of a final dosage
form 2002 for administering a medicament, such as the medicament
190 as previously described, to an animal, such as the animal 198
as previously described. The final dosage form includes means 2010
for entrapping at least one molecule of the medicament. The final
dosage form also includes means 2020 for controlling an
availability of the entrapped at least one molecule of medicament,
wherein the entrapped at least one molecule of medicament is
initially substantially not bioavailable if the final dosage form
is administered to the animal. The availability of the entrapped
medicament is modifiable ex vivo by an exposure to a stimulus, such
as the stimulus 192 described above, to be substantially
bioavailable if the final dosage form is administered to the
animal. The final dosage form further includes means 2030 for
protecting the means 2010 for entrapping at least one molecule of
the medicament from an ex vivo environment of the final dosage
form. The final dosage form also includes the medicament 190.
[0222] In an embodiment, the means 2020 for controlling an
availability of the entrapped at least one molecule of medicament
includes means 2022 for controlling an availability of the
entrapped at least one molecule of medicament and having a
premodification characteristic resulting in an insignificant uptake
in the gastrointestinal tract of the animal. In an embodiment, the
final dosage form further includes means 2050 for indicating an
exposure to the stimulus by the means for controlling an
availability of the entrapped at least one molecule of medicament.
In an embodiment, the final dosage form further includes means 2060
for containing the medicament within the final dosage form before
the final dosage form is administered to the animal. In an
embodiment, the final dosage form further includes means 2070 for
carrying the final dosage form into the animal.
[0223] FIG. 27 illustrates an example system 2100. The system
includes a final dosage form holder 2110 configured to carry at
least one instance of a final dosage form, illustrated as final
dosage form holder portions 2102A-2102C. The system also includes
the stimulus source 194 having at least one controllable stimulus
parameter or characteristic, operable to generate the stimulus 192,
and configured to direct the stimulus toward at least a portion of
the final dosage form holder. In an embodiment, the stimulus
generator is operable to direct the stimulus toward a selectable
portion of the final dosage form holder, such as the portion 2102A,
or a portion of the portion 2102A. The system further includes a
stimulation controller 2140 operable to regulate a controllable
parameter of the stimulus source. In an embodiment, the stimulation
controller is operable to regulate the controllable stimulus
parameter by regulating the stimulus source, by regulating a
stimulus transmission pathway between the stimulus source and the
final dosage form holder, or by regulating which spatial portion of
the dosage form receives the stimulus.
[0224] The system 2100 also includes a stimulation initiation
circuit 2160 operable to initiate a stimulus 192 having a selected
stimulus parameter or characteristic in response to a received
input. In an embodiment, the stimulation initiation circuit is
configured to transmit using the user interface 2195 a human
perceivable indication of an assessed quality or quantity of the
stimulus received by a final dosage form. The stimulation
initiation circuit may receive input from a human 2199, such as
pharmacist or health care provider, or from a stimulus assessment
circuit 2150. The stimulus assessment circuit is operable to
monitor the stimulus received by a final dosage form in response to
data received from an indicator monitoring circuit 2120. The
indicator monitoring circuit is operable to monitor an indicator
substance portion of the at least one instance of the final dosage
form. In an embodiment, the stimulus assessment circuit is operable
to generate a signal usable to provide a human perceivable
indication of the assessed stimulus received by a final dosage form
via the user interface.
[0225] In an embodiment, the system 2100 includes a final dosage
form recognizer circuit 2130 operable to generate data usable in
distinguishing a final dosage form. In an embodiment, the system
includes a release-state selection circuit 2165. In an embodiment,
the release-state selection circuit is responsive to signals
indicative of a chosen medicament bioavailability of a final dosage
form. In an embodiment, the release-state selection circuit is
responsive to a human 2199 initiated input entered into the user
interface 2195. In an embodiment, the system includes a stimulus
selection circuit 2170. In an embodiment, the stimulus selection
circuit is responsive to data generated by the final dosage form
recognizer circuit. In an embodiment, the stimulus selection
circuit is responsive to a human 2199 initiated input.
[0226] In an embodiment, the system 2100 includes a
computer-readable storage medium 2180 configured by a final dosage
form and stimulus exposure database 2182. The final dosage form and
stimulus exposure database may include instructions for
modification or state transformation of the final dosage form for
an efficacious administration to an animal by an exposure of the
final dosage form to a stimulus, such as the instructions 670 of
FIG. 6, the instructions 1270 of FIG. 17, or the instructions 1770
of FIG. 22. The final dosage form and stimulus exposure database
may include instructions for modification or state transformation
of the final dosage form for an efficacious administration to an
animal by an exposure of the final dosage form to the stimulus,
such as electronically published instructions, or such as indicated
by a reference book, such as Physician's Desk Reference. The final
dosage form and stimulus exposure database may include an
electronically-stored database relating stimuli and
medicament-bioavailability of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-bioavailability of the final dosage form and
stimuli.
[0227] In an embodiment, the system 2100 may be used to modify or
transform a bioavailability of a medicament associated with a final
dosage form described herein. For example, the system may be used
to modify or transform a bioavailability of a medicament associated
with the final dosage form 102 described in conjunction with FIG.
1; the final dosage form 202 described in conjunction with FIG. 2;
with the final dosage form 302 described in conjunction with FIG.
3; with the final dosage form 402 described in conjunction with
FIG. 4; with the final dosage form 502 described in conjunction
with FIG. 5; with the final dosage form 602 described in
conjunction with FIG. 6; with the final dosage form 1002 described
in conjunction with FIG. 15; with the final dosage form 1102
described in conjunction with FIG. 16; with the final dosage form
1202 described in conjunction with FIG. 17; with the final dosage
form 1502 described in conjunction with FIG. 20; with the final
dosage form 1702 described in conjunction with FIG. 22; or with the
final dosage form 1802 described in conjunction with FIG. 23.
[0228] In an embodiment, the system 2100 may be used to implement
an operational flow modifying or transforming a bioavailability of
a medicament associated with a final dosage form described herein.
For example, the system may be used to implement the example
operational flow 700 modulating a medicament-release characteristic
of a final dosage form described in conjunction with FIG. 7; the
example operational flow 800 fulfilling a request specifying a dose
of a medicament for an individual animal described in conjunction
with FIG. 9; the example operational flow 1300 modifying a
medicament availability characteristic of a final dosage form
described in conjunction with FIG. 18; or the example operation
flow 1910 described in conjunction with FIG. 24.
[0229] FIG. 28 illustrates an example environment 2200. The
environment includes a final dosage form 2210 for administering the
medicament 190 to the animal 198. The final dosage form includes a
particle or polymeric 2202 carrying the medicament in a first
medicament-release state wherein the medicament is available to the
animal in a first bioavailability if the final dosage form is
administered to the animal. The particle or polymeric material is
modifiable ex vivo by an exposure to a stimulus, such as the
stimulus 192 to carry the medicament in a second medicament-release
state wherein the medicament is available to the animal in a second
bioavailability if the final dosage form is administered to the
animal.
[0230] The particle or polymeric material may include a gel,
illustrated as a hydrogel 2202A, carrying a medicament 190A in a
first medicament-release state wherein the medicament is available
to the animal in a first bioavailability if the final dosage form
is administered to the animal. The particle or polymeric material
may include a liposome, illustrated as a liposome 2202B, carrying a
medicament 190B in a first medicament-release state wherein the
medicament is available to the animal in a first bioavailability if
the final dosage form is administered to the animal. The particle
or polymeric material may include a nanoparticle, illustrated as a
nanosphere 2202C, carrying a medicament 190C in a first
medicament-release state wherein the medicament is available to the
animal in a first bioavailability if the final dosage form is
administered to the animal.
[0231] In an embodiment, the first bioavailability to the animal
198 includes a first bioavailability characteristic to the animal
and the second bioavailability to the animal includes a second
bioavailability characteristic. In an embodiment, the first
bioavailability characteristic includes the medicament 190 having a
bioavailability in the small intestine of the animal, and the
second bioavailability characteristic includes the medicament
having a bio availability in the large intestine of the animal. In
an embodiment, the first bioavailability characteristic includes
the medicament having a first medicament quantity available to the
animal, and the second bioavailability characteristic includes the
medicament having a second medicament quantity available to the
animal. For example, the first medicament quantity may be 100 mg
and the second medicament quantity may be 200 mg. In an embodiment,
the first bioavailability characteristic includes the medicament
having an immediate release medicament quantity available to the
animal, and the second bioavailability characteristic includes the
medicament having a time-release medicament quantity available to
the animal. In an embodiment, the first bioavailability
characteristic includes the medicament having a first time-release
rate, and the second bioavailability characteristic includes the
medicament having a second time-release rate. In an embodiment, the
first bioavailability characteristic includes the medicament having
a first release-decay rate medicament release to the animal, and
the second bioavailability characteristic includes the medicament
having a second release-decay rate medicament release to the
animal. In an embodiment, the first bioavailability characteristic
includes the medicament having a first pH sensitivity, and the
second bioavailability characteristic includes the medicament
having a second pH sensitivity.
[0232] In an embodiment, the first bioavailability to the animal
198 includes a first bioavailability characteristic to the animal
and the second bioavailability to the animal includes a second
bioavailability characteristic. In this embodiment, the second
bioavailability characteristic to the animal may include a
substantially different bioavailability characteristic to the
animal than the first bioavailability characteristic to the animal.
In an alternative of this embodiment, the first bioavailability
characteristic to the animal includes a first medicament dosage and
the second bioavailability characteristic to the animal includes a
second medicament dosage. In another alternative of this
embodiment, the first bioavailability characteristic to the animal
includes a first medicament release kinetic and the second
bioavailability characteristic to the animal includes a second
medicament release kinetic. In a further alternative of this
embodiment, the first bioavailability characteristic to the animal
includes a first medicament release profile and the second
bioavailability characteristic to the animal includes a second
medicament release profile. In an alternative of this embodiment,
the first bioavailability characteristic to the animal includes a
first medicament release rate and the second bioavailability
characteristic to the animal includes a second medicament release
rate. In another alternative of this embodiment, the first
bioavailability characteristic to the animal includes a first
medicament release delay time and the second bioavailability
characteristic to the animal includes a second medicament release
delay time. In a further alternative of this embodiment, the first
bioavailability characteristic to the animal includes a first
medicament release pH dependence and the second bioavailability
characteristic to the animal includes a second medicament release
pH dependence.
[0233] In an embodiment, the particle or polymeric material 2202
carrying the medicament 190 includes an inert particle or polymeric
material carrying the medicament. In an embodiment, the particle or
polymeric material carrying the medicament includes a particle or
polymeric material carrying the medicament in an association. In an
embodiment, the particle or polymeric material carrying the
medicament includes a particle or polymeric material encapsulating
the medicament. In an embodiment, the particle or polymeric
material carrying the medicament includes a particle or polymeric
material encompassing the medicament. In an embodiment, the
particle or polymeric material carrying the medicament includes a
particle or polymeric material at least one of engaging, retaining,
or binding the medicament. In an embodiment, the particle or
polymeric material carrying the medicament includes a particle or
polymeric material carrier conjugated with the medicament. In an
embodiment, the particle or polymeric material carrying the
medicament includes the medicament taken-up by the particle or
polymeric material.
[0234] In an embodiment, the final dosage form 2210 further
includes a transport medium 2280 suitable for delivering the
particle or polymeric material binding the medicament to the
animal. In an embodiment, the transport medium may include a
carrier, admixture, diluent, or excipient. In an embodiment, the
final dosage form includes an indicator substance (not illustrated)
associated with the particle or polymeric material and configured
to indicate an exposure to the stimulus of the particle or
polymeric material carrying the medicament.
[0235] FIG. 29 illustrates an example environment 2300. The example
environment includes a final dosage form 2310 for administering the
medicament 190 to the animal 198. The final dosage form includes a
dosage portion labeled as "A Portion" carrying a medicament 190A in
a first medicament-release state wherein the medicament is
bioavailable to the animal if the final dosage form is administered
to the animal. In an embodiment, the dosage portion "A" includes a
chamber 2320A defining a chamber periphery 2322A. The final dosage
portion includes another dosage portion labeled as "B Portion"
carrying another medicament 190B and including a release element
2330B in a first medicament-release state wherein the another
medicament has a first bioavailability to the animal if the final
dosage form is administered to the animal in the first
medicament-release state. The release element is modifiable ex vivo
to second medicament-release state by an exposure to stimulus,
wherein the another medicament has a second bioavailability to the
animal if the final dosage form is administered to the animal in
the second medicament-release state. In an embodiment, the dosage
portion "B" includes a chamber 2320B defining a chamber periphery
2322B.
[0236] FIG. 30 illustrates an example environment 2400 that
includes a final dosage form 2405 and an operational flow 2410. The
final dosage form includes a medicament. The final dosage form also
includes a particle or polymeric material carrying the medicament
in a first medicament-release state wherein the medicament is
available to the animal in a first bioavailability if the final
dosage form is administered to the animal. The particle or
polymeric material is modifiable ex vivo by an exposure to a
stimulus to carry the medicament in a second medicament-release
state wherein the medicament is available to the animal in a second
bioavailability if the final dosage form is administered to the
animal. In an embodiment, the final dosage form may be implemented
using the final dosage form 2210 described in conjunction with FIG.
28.
[0237] The operational flow 2410 includes, after a start operation,
a modification operation 2420. The modification operation includes
transforming the particle or polymeric material to the second
medicament-release state by initiating an ex vivo exposure of the
particle or polymeric material to the stimulus. The operational
flow includes an end operation. In an embodiment, the modification
operation 2420 may be implemented using the system 2100 described
in conjunction with FIG. 27.
[0238] FIG. 31 illustrates an example article of manufacture 2502
for administering medicament to an animal. The article includes
means 2510 for releasably encompassing a medicament in a first
state wherein the medicament is available to the animal in a first
bioavailability if the final dosage form is administered to the
animal. The means for releasably encompassing the medicament in a
first state is modifiable ex vivo by an exposure to a stimulus to
releasably encompass the medicament in a second state, wherein the
medicament is available to the animal in a second bioavailability
if the final dosage form is administered to the animal. The article
also includes the medicament 190.
[0239] In an embodiment, the article 2502 includes means 2530 for
protecting the means 2510 for releasably encompassing the
medicament in a first state. In an embodiment, the article includes
means 2550 for indicating an exposure to the stimulus of the means
for releasably encompassing the medicament in a first state. In an
embodiment, the article includes means 2560 for containing the
medicament within the final dosage form before the final dosage
form is administered to the animal. In an embodiment, the article
includes means 2570 for carrying the final dosage form into the
animal.
[0240] FIG. 32 illustrates an example environment 2600. The
environment includes a final dosage form 2610 for administering
medicament 190 to the animal 198. The final dosage form includes a
release-control substance 2602 carrying the medicament in a first
medicament-release state wherein the medicament has a first
bioavailability to the animal if the final dosage form is
administered to the animal. The release-control substance is
modifiable ex vivo by an exposure to a first stimulus, such as a
first stimulus 192A (not separately shown) of the stimulus 192, to
carry the medicament in a second medicament-release state wherein
the medicament has a second bioavailability to the animal if the
final dosage form is administered to the animal. The
release-control substance is modifiable ex vivo by an exposure to
second stimulus, such as a second stimulus 190B (not shown) of the
stimulus 192, to carry the medicament in a third medicament-release
state wherein the medicament has a third bioavailability to the
animal if the final dosage form is administered to the animal. The
final dosage form also includes the medicament 190.
[0241] The release-control substance 2602 may include a gel,
illustrated as a hydrogel 2602A carrying a medicament 190A in a
first medicament-release state wherein the medicament is available
to the animal in a first bioavailability if the final dosage form
is administered to the animal. The release-control substance may
include a liposome, illustrated as a liposome 2602B carrying a
medicament 190B in a first medicament-release state wherein the
medicament is available to the animal in a first bioavailability if
the final dosage form is administered to the animal. The
release-control substance may include a nanoparticle, illustrated
as a nanosphere 2602C carrying a medicament 190C in a first
medicament-release state wherein the medicament is available to the
animal in a first bioavailability if the final dosage form is
administered to the animal.
[0242] In an embodiment, the first bioavailability to the animal
198 includes the medicament 190 being substantially not
bioavailable to the animal. In an embodiment, the first
bioavailability to the animal includes the medicament being
substantially bioavailable to the animal. In this embodiment, the
second bioavailability to the animal may include the medicament
being substantially bioavailable to the animal, wherein the second
bioavailability to the animal is substantially different from the
first bioavailability to the animal. In an embodiment, the second
bioavailability to the animal includes the medicament being
substantially not bioavailable to the animal. In an embodiment, the
second bioavailability to the animal includes the medicament being
substantially bioavailable to the animal. In an embodiment, the
third bioavailability to the animal includes the medicament being
substantially not bioavailable to the animal. In an embodiment, the
third bioavailability to the animal includes the medicament being
substantially bioavailable to the animal.
[0243] In an embodiment, the third bioavailability to the animal
198 includes the medicament 190 being substantially bioavailable to
the animal, wherein the third bioavailability to the animal is
substantially different from the second bioavailability to the
animal. For example, the third bioavailability may be substantially
different from the second bioavailability in dosage amount, dosage
rate, or dosage profile. In an embodiment, the third
bioavailability to the animal includes the medicament being
substantially bioavailable to the animal, wherein the third
bioavailability is substantially different from both the first
bioavailability and the second bioavailability. In an embodiment,
the first bioavailability includes a first bioavailability
characteristic, the second bioavailability includes a second
bioavailability characteristic, and the third bioavailability
includes a third bioavailability characteristic.
[0244] In an embodiment, the release-control substance 2602
includes a biocompatible substance. In an embodiment, a
biocompatible substance includes a substance having a quality of
not having toxic or injurious effects on biological systems of the
animal. In another embodiment, a biocompatible substance includes a
substance that does not elicit any undesirable local or systemic
effects in the animal. In an embodiment, the release-control
substance includes a release-control substance having a modifiable
medicament release characteristic. In an embodiment, the
release-control substance includes a release-control substance
carrying the medicament 190 in an initial medicament-retention
state. In an embodiment, the release-control substance includes a
particle. In an embodiment, the release-control substance includes
a polymeric material. In an embodiment, the release-control
substance includes a small molecule. In an embodiment, the
release-control substance includes a capsule structure.
[0245] In an embodiment, the second stimulus 192B (not separately
shown) includes a substantially different category of stimulus than
the first stimulus 192A. In an embodiment, the second stimulus has
at least a substantially different intensity than the first
stimulus. In an embodiment, the second stimulus includes a
substantially different duration than the first stimulus. In an
embodiment, the second stimulus includes a substantially different
waveform than the first stimulus.
[0246] In an embodiment, the release-control substance 2602
includes a release-control substance modifiable ex vivo by an
exposure of a first portion of the release-control substance to the
first stimulus 192A to carry the medicament in a second
medicament-release state. In this embodiment, the release-control
substance includes a release-control substance modifiable ex vivo
by an exposure of a second portion of the release-control substance
to the second stimulus 192B to carry the medicament in a third
medicament-release state.
[0247] In an embodiment, the final dosage form 2610 includes a
transport medium 2680 configured to facilitate administering the
medicament and the release-control substance to the animal. In an
embodiment, the final dosage form includes an indicator substance
(not shown) configured to indicate an exposure of at least a
portion of the release-control substance to at least one of the
first stimulus or the second stimulus. In an embodiment, the final
dosage form includes an in vivo degradable containment element (not
shown) configured to retain the release-control substance until the
final dosage form is administered to the animal.
[0248] The following table illustrates several states of an example
of the final dosage form 2610:
TABLE-US-00001 TABLE 1 Example bioavailability configurations 1-3
Bioavailability of Bioavailability of Bioavailability of medicament
in a medicament in a medicament in a Release control final dosage
form final dosage form final dosage form substance state
configuration #1 configuration #2 configuration #3 First 1 0 0
medicament- release state Modified to 0 1 2 second medicament-
release state Modified to 2 2 1 third medicament- release state 0 =
the medicament is substantially not bioavailable 1 = the medicament
is substantially bioavailable 2 = the medicament is substantially
bioavailable in a characteristic substantially different that in
1
[0249] FIG. 33 illustrates an example environment 2700 that
includes an article of manufacture 2701. The article of manufacture
includes a final dosage form 2710 for administering medicament to
the animal 198. The final dosage form includes the medicament 190
(not shown). The final dosage form also includes a release-control
substance carrying the medicament in a first medicament-release
state wherein the medicament has a first bioavailability to the
animal if the final dosage form is administered to the animal. The
release-control substance is modifiable ex vivo by an exposure to a
first stimulus to carry the medicament in a second
medicament-release state wherein the medicament has a second
bioavailability to the animal if the final dosage form is
administered to the animal. The release-control substance is
modifiable ex vivo by an exposure to a second stimulus to carry the
medicament in a third medicament-release state wherein the
medicament has a third bioavailability to the animal if the final
dosage form is administered to the animal. In an embodiment, the
final dosage form includes a transport medium 2780 configured to
facilitate administering the medicament and the release-control
substance to the animal. In an embodiment, the final dosage form
may be substantially similar to the final dosage form 2610
described in conjunction with FIG. 32. The article of manufacture
also includes instructions 2770 specifying an ex vivo exposure of
the release-control substance to the first stimulus or to the
second stimulus to achieve a selected second medicament release
state or a selected third medicament-release state.
[0250] In an embodiment, the instructions 2770 include instructions
specifying an ex vivo exposure of the release-control substance to
a selected first stimulus or to a selected second stimulus, such
that when implemented transform the release-control substance to
the selected second medicament-release state or the selected third
medicament-release state.
[0251] FIG. 34 illustrates an example environment 2800 that
includes a final dosage form 2805 and an operational flow 2810. The
final dosage form includes a medicament. The final dosage form also
includes a release-control substance carrying the medicament in a
first medicament-release state wherein the medicament has a first
bioavailability to the animal if the final dosage form is
administered to the animal. The release-control substance is
modifiable ex vivo by an exposure to a first stimulus to carry the
medicament in a second medicament-release state wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal. The release-control
substance is modifiable ex vivo by an exposure to second stimulus
to carry the medicament in a third medicament-release state wherein
the medicament has a third bioavailability to the animal if the
final dosage form is administered to the animal. In an embodiment,
the final dosage form 2805 is substantially similar to the final
dosage form 2610 described in conjunction with FIG. 32.
[0252] After a start operation, the operational flow includes an
individualization operation 2820. The individualization operation
includes transforming the medicament release state of the
release-control substance of the final dosage form 2805 to the
second medicament-release state or the third medicament-release
state by initiating an ex vivo exposure of the release-control
substance respectively to the first stimulus or the second
stimulus. The operational flow includes an end operation. In an
embodiment, the operational flow 2810 may be implemented using the
system 2100 described in conjunction with FIG. 27.
[0253] FIG. 35 illustrates an alternative embodiment of the
individualization operation 2820 of FIG. 34. The individualization
operation may include at least one additional operation. The at
least one additional operation includes an operation 2822, or an
operation 2824. The operation 2822 includes modifying the
medicament release state of the release-control substance to the
second medicament-release state or the third medicament-release
state by initiating an ex vivo exposure of the release-control
substance respectively to the first stimulus or the second
stimulus. In an embodiment, the operational 2282 may be implemented
using the system 2100 described in conjunction with FIG. 27. The
operation 2824 includes transforming the medicament release state
of the release-control substance to the second medicament-release
state or the third medicament-release state by initiating an ex
vivo exposure of the release-control substance to a stimulus
selected respectively from the first stimulus or the second
stimulus. In an embodiment, the operation 2822 may be implemented
using the stimulus selection circuit 2165 described in conjunction
with FIG. 21.
[0254] FIG. 36 illustrates an alternative embodiment of the
individualization operation 2820 of FIG. 34. The individualization
operation may include at least one additional operation. The at
least one additional operation includes an operation 2832, an
operation 2834, or an operation 2836. The operation 2832 includes
initiating an ex vivo exposure of the release-control substance
respectively to a modification stimulus selected from the first
stimulus or the second stimulus. The selected modification stimulus
having a parameter operative to transform the release-control
substance carrying the medicament from the first medicament-release
state to the second medicament-release state or to the third
medicament-release state. The operation 2834 includes initiating an
ex vivo exposure of the release-control substance to a modification
stimulus selected from the first stimulus or the second stimulus,
the selected modification stimulus operative to transform the
release-control substance carrying the medicament from the first
medicament-release state to the second medicament-release state or
from the first medicament-release state to the third
medicament-release state. The operation 2836 includes initiating an
ex vivo exposure of the release-control substance respectively to a
stimulus selected from the first stimulus or the second stimulus,
the selected stimulus having at least one of a stimulation
characteristic or a spatial characteristic operable to transform
the release-control substance carrying the medicament from the
first medicament-release state to the second medicament-release
state or to the third medicament-release state. For example, a
stimulation characteristic may include a waveform, duration, or
intensity. A spatial characteristic may include initiating an ex
vivo exposure of a portion of the release-control substance to the
stimulus.
[0255] The operations 2832, 2834, or 2286 may be implemented using
the stimulus selection circuit 2170 described in conjunction with
FIG. 21. In another embodiment, the operation 3972 may be
implemented using a combination of the stimulus selection circuit
2170, the computing device 2175, and/or the final dosage form and
stimulus exposure database 2182 described in conjunction with FIG.
21.
[0256] FIG. 37 illustrates an alternative embodiment of the
operational flow 2810 of FIG. 34. The operational flow 2810 may
include at least one additional operation, such as a choosing
operation 2850. The choosing operation includes selecting a
medicament-release state from the second medicament-release state
and the third medicament-release state in response to a chosen
medicament bioavailability of the final dosage form. The choosing
operation may be implemented using the release-state selection
circuit 2165 described in conjunction with FIG. 27. In an
embodiment, the stimulus selection circuit 2170, the computing
device 2175, and/or the final dosage form and stimulus exposure
database 2182 (saved on the computer-readable storage medium 2180)
may cooperatively implement the choosing operation. The choosing
operation may include at least one additional operation, such as an
operation 2860. The operation 2860 includes selecting a
modification stimulus from the first stimulus and the second
stimulus in response to the selected medicament-release state. The
operation 2860 may be implemented using the stimulus selection
circuit 2170 described in conjunction with FIG. 27. In an
embodiment, the stimulus selection circuit, the computing device
2175, and/or the final dosage form and stimulus exposure database
2182 may cooperatively implement the operation 2860.
[0257] FIG. 38 illustrates an example environment 2900 that
includes a final dosage form 2905 and an operational flow 2910. The
final dosage form includes a medicament. The final dosage form also
includes a release-control substance carrying the medicament in a
medicament-retention state wherein the medicament is substantially
not bioavailable to the animal if the final dosage form is
administered to the animal. The release-control substance is
modifiable ex vivo by an exposure to a first stimulus to carry the
medicament in a first medicament-release state wherein the
medicament has a first bioavailability to the animal if the final
dosage form is administered to the animal. The release-control
substance is modifiable ex vivo by an exposure to a second stimulus
to carry the medicament in a second medicament-release state
wherein the medicament has a second bioavailability to the animal
if the final dosage form is administered to the animal. In an
embodiment, the final dosage form 2905 may be substantially similar
to the final dosage form 2610 described in conjunction with FIG.
32.
[0258] After a start operation, the operational flow includes a
release state choosing operation 2920. The release state choosing
operation includes automatically selecting a medicament-release
state from the first medicament-release state and the second
medicament-release state based on a specified medicament
bioavailability of the final dosage form. In an embodiment, the
specified medicament bioavailable may be indicated by a physician's
prescription, a request by a person to receive the final dosage
form, or a table. In an embodiment, the release state choosing
operation may be implemented using the system 2100 described in
conjunction with FIG. 27. For example, the person 2199 may enter a
prescription of 500 mg of penicillin into the user interface 2195.
In response thereto, the release-state selection circuit 2165 of
the system automatically selects a medicament-release state to
achieve 500 mg of penicillin from the first medicament-release
state and the second medicament-release state based on the
specified medicament bioavailability of the final dosage form. In
an embodiment, the selection may be facilitated using the computing
device 2175 and information provided by the final dosage form, and
stimulus exposure database 2182 described in conjunction with FIG.
27.
[0259] A stimulus choosing operation 2930 includes automatically
selecting a stimulus from the first stimulus and the second
stimulus in response to the selected medicament-release state. In
an embodiment, the stimulus choosing operation may be implemented
using the system 2100 described in conjunction with FIG. 27. For
example, the stimulus selection circuit 2170 may implement the
stimulus choosing operation. In an embodiment, the stimulus
choosing operation may be implemented in part, in whole by, or in
cooperation with the computing device 2175, and/or the final dosage
form and stimulus exposure database 2182. A dosage configuration
operation 2940 includes transforming the medicament release state
of the release-control substance by initiating an ex vivo exposure
of the release-control substance to the selected stimulus. In an
embodiment, the dosage configuration operation may be implemented
using the system 2100 described in conjunction with FIG. 27. For
example, the stimulus initiation circuit 2160 may initiate the ex
vivo exposure of the release-control substance to the selected
stimulus 192 generated by the stimulus source 194. The operational
flow includes an end operation.
[0260] FIG. 39 illustrates an example vehicle 3002 for
administering a medicament to the animal 198. The vehicle including
means 3010 for releasably encompassing the medicament in a first
medicament-release state wherein the medicament has a first
bioavailability to the animal if the vehicle is administered to the
animal. The means for releasably encompassing the medicament in a
first medicament-release state is modifiable to a second
medicament-release state upon an ex vivo exposure to a first
stimulus, the medicament in the second medicament-release state
having a second bioavailability to the animal if the vehicle is
administered to the animal. The means for releasably encompassing
the medicament in a first medicament-release state is modifiable to
a third medicament-release state upon an ex vivo exposure to a
second stimulus, the medicament in the third medicament-release
state having a third bioavailability to the animal if the vehicle
is administered to the animal. The vehicle also includes the
medicament 190.
[0261] In an embodiment, the vehicle includes means 3030 for
protecting the means for releasably encompassing the medicament
against an ex vivo environment. In an embodiment, the vehicle
includes means 3050 for indicating an exposure of the means for
releasably encompassing the medicament to the first stimulus or the
second stimulus. In an embodiment, the vehicle includes means 3060
for containing the medicament within the vehicle before the final
dosage form is administered to the animal. In an embodiment, the
vehicle includes means 3070 for carrying the vehicle into the
animal.
[0262] Returning to FIG. 27, FIG. 27 illustrates another example of
system 2100. The system includes the computer-readable storage
medium 2180 configured to indicate a stimulus to modify ex vivo a
bioavailability of a medicament carried by a final dosage form
based upon a selected medicament bioavailability of the final
dosage form. The system also include a holder 2110 configured to
establish ex vivo of the animal a location of a final dosage form
to receive the indicated stimulus 192 from a stimulus source 194.
The system further includes the stimulus source operable to provide
the indicated stimulus. The system also includes a stimulation
controller 2140 operable to regulate an ex vivo exposure of a final
dosage form to the indicated stimulus.
[0263] In an embodiment, the computer-readable storage medium 2180
includes a computer-readable storage medium configured to indicate
a stimulus to modify ex vivo a bioavailability of a medicament
carried by a final dosage form based upon a selected medicament
bioavailability of the final dosage form. The indicated stimulus
includes at least one of a type, time, intensity, wave form, or
pulse form characteristic of the stimulus. In an embodiment, the
computer-readable storage medium includes a computer-readable
storage medium configured to indicate a stimulus to modify ex vivo
a bioavailability of a medicament carried by a final dosage form
based upon a selected medicament bioavailability of the final
dosage form. The computer-readable storage medium is also
configured to indicate another stimulus to modify ex vivo a
bioavailability of another medicament carried by another final
dosage form based upon another selected medicament bioavailability
of the another final dosage form. In an embodiment, the
computer-readable storage medium includes a computer-readable
storage medium configured to indicate a stimulus to modify ex vivo
a bioavailability of a medicament carried by a final dosage form
based upon a selected medicament bioavailability of the final
dosage form. The computer-readable storage mediums is also
configured to indicate another stimulus to modify ex vivo a
bioavailability of the medicament carried by a final dosage form
based upon the selected medicament bioavailability of the final
dosage form. In an embodiment, the computer-readable storage medium
includes a computer-readable storage medium configured to indicate
a stimulus to that is at least one of sufficient, effective, or
operable modify ex vivo a bioavailability of a medicament carried
by a final dosage form based upon a selected medicament
bioavailability of the final dosage form.
[0264] In an embodiment, the computer-readable storage medium 2180
includes a computer-readable storage medium configured to indicate
a stimulus 192 operable to modify ex vivo a bioavailability of a
medicament carried by a final dosage form based upon a selected
medicament bioavailability of the final dosage form. In an
embodiment, the computer-readable storage medium includes a
computer-readable storage medium configured to indicate a stimulus
to substantially modify ex vivo a bioavailability of a medicament
carried by a final dosage form based upon a selected medicament
bioavailability of the final dosage form. In an embodiment, the
computer-readable storage medium includes a computer-readable
storage medium configured to indicate a stimulus to modify ex vivo
a bioavailability of a medicament carried by a final dosage form
based upon a selected treatment using the final dosage form. In an
embodiment, the computer-readable storage medium includes a
computer-readable storage medium configured to indicate a stimulus
to modify ex vivo a bioavailability of a medicament carried by a
final dosage form based upon a selected efficacious treatment using
the final dosage form.
[0265] In an embodiment, the holder 2110 includes a holder operable
to locate a final dosage form in a position to receive the
indicated stimulus 192 from a stimulus source 194 before an
administration of the final dosage form to the animal 192. In an
embodiment, the holder includes a holder operable to establish a
location of a final dosage form to receive the indicated stimulus
from a stimulus source and ex vivo of the animal. In an embodiment,
the holder includes a holder operable to establish ex vivo of the
animal a location of at least two instance of a final dosage form
to receive the indicated stimulus from a stimulus source.
[0266] In an embodiment, the stimulus source 194 includes a
stimulus device, circuit, module, or generator operable to provide
the indicated stimulus 192 for a final dosage form. In an
embodiment, the stimulus source includes a stimulus source operable
to produce the indicated stimulus. In an embodiment, the stimulus
source includes a stimulus source operable to generate the
indicated stimulus. In an embodiment, the stimulus source includes
a stimulus source operable to provide the indicated stimulus to at
least two instances of the final dosage form. In an embodiment, the
stimulus source includes a stimulus source operable to provide the
indicated stimulus. The indicated stimulus includes at least one of
a mechanical stimulus, a non-ionizing radiation stimulus, an
ionizing radiation stimulus, a chemical stimulus, an acoustic
stimulus, an ultrasound stimulus, a radio wave stimulus, a
microwave stimulus, a light wave stimulus, or a thermal stimulus.
In an embodiment, the stimulus source includes a stimulus source
operable to provide an indicated stimulus having at least one
controllable characteristic. In an embodiment, the stimulus source
includes a stimulus source operable to provide the indicated
stimulus and to direct the provided stimulus at a portion of the
location of a final dosage form established by the holder. In an
alternative of the this embodiment, the stimulus source is operable
to provide the indicated stimulus and to direct the provided
stimulus at a selectable portion of the location of a final dosage
form established by the holder. In an embodiment, the stimulus
source includes a stimulus source operable to provide the indicated
stimulus for a final dosage form and for another final dosage form.
In an embodiment, the stimulus source includes a stimulus source
operable to provide the indicated stimulus for at least two
instances of a final dosage form.
[0267] In an embodiment, the stimulation controller 2140 includes a
stimulation controller operable to regulate the stimulus source 194
in response to a received human-initiated activation input. In an
embodiment, the stimulation controller includes a stimulation
controller operable to regulate the stimulus source in response to
a received feedback device-initiated activation input. In an
embodiment, the stimulation controller includes a stimulation
controller operable to regulate the stimulus source in response to
a received stimulus-selector initiated activation input. In an
embodiment, the stimulation controller includes a stimulation
controller operable to regulate the stimulus source in response to
a received activation input indicating a selected stimulus. In an
embodiment, the stimulation controller includes a stimulation
controller operable to regulate the stimulus source in response to
the indicated stimulus for a final dosage form and in response to a
received activation input. In an embodiment, the stimulation
controller includes a stimulation controller device, circuit,
module, or programmed device operable to regulate an ex vivo
exposure of a final dosage form to the indicated stimulus. In an
embodiment, the stimulation controller includes a stimulation
controller operable to regulate a stimulus transmission pathway
between the stimulus source and the holder in response to the
indicated stimulus for a final dosage form. In an embodiment, the
stimulation controller includes a stimulation controller operable
to regulate the stimulus source and direct the stimulus toward a
selected portion of a final dosage form carried by the holder 2110
in response to the indicated stimulus for the final dosage form,
and in response to a received activation input.
[0268] In an embodiment, the stimulation controller 2140 includes a
stimulation controller operable to regulate a duration of the
stimulus, a wave characteristic of the stimulus, an intensity of
the stimulus, a density of the stimulus, or amplitude of the
stimulus source in response to the indicated stimulus for a final
dosage form. In an embodiment, the wave characteristic may include
a pulse form or a dynamic waveform.
[0269] In an embodiment, the system 2100 further includes a
stimulus assessment circuit 2150 operable to monitor an aspect of
the indicated stimulus 192 provided by the stimulus source 194. In
an embodiment, the stimulus assessment circuit includes a stimulus
assessment circuit operable to monitor an aspect of the indicated
stimulus received by a final dosage form. In an embodiment, the
stimulus assessment circuit includes a stimulus assessment circuit
operable to monitor at least one of a type, quantity, or a
characteristic of the indicated stimulus received by a final dosage
form. In an embodiment, the stimulus assessment circuit includes a
stimulus assessment circuit operable to monitor an aspect of the
indicated stimulus received by at least a portion of a final dosage
form. In an embodiment, the stimulus assessment circuit includes a
stimulus assessment circuit operable to monitor an aspect of an
indicator substance portion of a final dosage form. In an
embodiment, the stimulus assessment circuit includes a stimulus
assessment circuit operable to sense a parameter of a final dosage
form responsive to the indicated stimulus received by the final
dosage form. In an embodiment, the stimulus assessment circuit
includes a stimulus assessment circuit operable to monitor an
aspect of the indicated stimulus received by a final dosage form,
and to generate an output indicative of the monitored aspect of the
indicated stimulus received by the final dosage form. In this
embodiment, the stimulation controller 2140 includes a stimulation
controller operable to regulate an ex vivo exposure of a final
dosage form to the indicated stimulus in response to the generated
output indicative of the monitored aspect of the indicated stimulus
received by the final dosage form. In an alternative embodiment,
the stimulus assessment circuit includes a stimulus assessment
circuit operable to monitor an aspect of the indicated stimulus
received by a final dosage form, and to generate an output signal
indicative of the monitored aspect of the indicated stimulus
received by the final dosage form and receivable by the stimulation
controller 2140. In an embodiment, the stimulus assessment circuit
includes a stimulus assessment circuit operable to generate a
signal usable in providing a human perceivable indication of an
aspect of the indicated stimulus received by a final dosage
form.
[0270] In an embodiment, the system 2100 further includes an
indicator monitoring circuit 2120 operable to generate a signal
indicative of a status of an indicator substance associated with a
final dosage form and configured to indicate an exposure to the
indicated stimulus by the final dosage form. In an embodiment, the
indicator monitoring circuit includes an indicator monitoring
circuit operable to generate signal indicative of at least one of
an exposed, exposed to an extent, or not exposed status of an
indicator substance associated with a final dosage form and
configured to indicate an exposure to the indicated stimulus by the
final dosage form. In an embodiment, the indicator monitoring
circuit includes an indicator monitoring circuit operable to
generate a human perceivable indication of a status of an indicator
substance associated with a final dosage form and configured to
indicate an exposure to the indicated stimulus by the final dosage
form. In an embodiment, the indicator monitoring circuit includes
an indicator monitoring circuit operable to generate a machine
readable signal indicative of a status of an indicator substance
associated with a final dosage form and configured to indicate an
exposure to the indicated stimulus by the final dosage form.
[0271] In an embodiment, the system 2100 further includes a
stimulus initiation circuit 2160 operable to initiate the provision
of the indicated stimulus by the stimulation source. In an
embodiment, the stimulus initiation circuit includes a stimulus
initiation circuit operable to initiate the provision of the
indicated stimulus by the stimulation source in response to at
least one of a received user input or an automatically generated
instruction. In an embodiment, the stimulus initiation circuit
includes a stimulus selection circuit operable to select the
indicated stimulus for provision by the stimulus source. In an
embodiment, the stimulus initiation circuit includes a stimulus
selection circuit operable to select the indicated stimulus for
provision by the stimulus source in response to at least one of a
received user input or in response to an automatically generated
input.
[0272] In an embodiment, the system 2100 further includes a final
dosage form recognizer circuit 2130 operable to generate data
indicative of an identifying characteristic of a final dosage form.
The data indicative of an identifying characteristic of the final
dosage form may be acquired in response to discernable aspect of
the final dosage form, such as a bar code, shape, color, or
marking.
[0273] FIG. 40 illustrates an example system 3100. The system
includes means 3110 for persistently storing computer-readable
information indicative of a stimulus operable to modify ex vivo a
bioavailability of a medicament carried by a final dosage form for
administration of the medicament to an animal. The system also
includes means 3120 for establishing ex vivo of the animal a
location of the final dosage form to receive the indicated stimulus
from a stimulus source. The system further includes means 3130 for
providing the indicated stimulus. The system also includes means
3140 for regulating an ex vivo exposure of the final dosage form to
the indicated stimulus.
[0274] In an embodiment, the means 3110 for persistently storing
computer-readable information includes means 3112 for persistently
storing computer-readable information indicative of a stimulus to
modify ex vivo a bioavailability of a medicament carried by a final
dosage form for administration of the medicament to an animal. The
computer-readable information indicative of a stimulus based upon a
selected medicament bioavailability of the final dosage form.
[0275] FIG. 41 illustrates an example environment 3200. The
environment includes a final dosage form 3202 for administering
medicament to the animal 198. The final dosage form includes a
dosage portion, illustrated as an "A" Portion. The dosage portion
has a chamber 3220A carrying a medicament 190A. The dosage portion
includes a release element 3230A in a first medicament-release
state. In the first medicament state, the medicament has a first
bioavailability to the animal if the final dosage form is
administered to the animal in the first medicament-release state.
The release element is modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus 192A (not
illustrated). In the second medicament-release state, the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal in the second
medicament-release state. The final dosage form includes another
dosage portion, illustrated as a "B" Portion. The another dosage
portion has another chamber 3220B carrying another medicament 190B.
The another dosage portion includes another release element 3230B
in another first medicament-release state. In the another first
medicament-release state, the another medicament has another first
bioavailability to the animal if the final dosage form is
administered to the animal in the another first medicament-release
state. The another release element is modifiable ex vivo to another
second medicament-release state by an exposure to another stimulus
192B (not illustrated). In the another second medicament-release
state, the another medicament has another second bioavailability to
the animal if the final dosage form is administered to the animal
in the another second medicament-release state. The final dosage
form includes an outer layer 3210 enclosing the dosage portion and
the another dosage portion.
[0276] In an embodiment, the first medicament-release state
includes a first medicament-release state wherein the medicament
190A is not bioavailable to the animal 198. In an embodiment, the
first medicament-release state includes a first medicament-release
state wherein the medicament is bioavailable to the animal. In an
embodiment, the second medicament-release state includes a second
medicament-release state wherein the medicament is not bioavailable
to the animal. In an embodiment, the second medicament-release
state includes a second medicament-release state wherein the
medicament is bioavailable to the animal.
[0277] In an embodiment, the another first medicament-release state
includes another first medicament-release state wherein the another
medicament 190B is not bioavailable to the animal 198. In an
embodiment, the another first medicament-release state includes
another first medicament-release state wherein the another
medicament is bioavailable to the animal. In an embodiment, the
another second medicament-release state includes another second
medicament-release state wherein the another medicament is not
bioavailable to the animal. In an embodiment, the another second
medicament-release state includes another second medicament-release
state wherein the another medicament is bioavailable to the
animal.
[0278] In an embodiment of the final dosage form 3202, if the first
medicament-release state includes the medicament 190A being
bioavailable to the animal and if the another first
medicament-release state includes the another medicament 190B being
bioavailable to the animal 198, a first ratio exists between the
bioavailability of the medicament and the bioavailability of the
another medicament. In this embodiment of the final dosage form, if
the second medicament-release state includes the medicament 190A
being bioavailable to the animal and if the another second
medicament-release state includes the another medicament 190B being
bioavailable to the animal, a second ratio exists between the
bioavailability of the medicament and the bioavailability of the
another medicament. In an embodiment, the first ratio is equal to
or greater than the second ratio. In an embodiment, the first ratio
is less than the second ratio.
[0279] In an embodiment of the final dosage form 3202, if the
second medicament-release state includes the medicament 190A being
bioavailable to the animal 198 and if the another second
medicament-release state includes the another medicament 190B being
bioavailable to the animal, a second ratio exists between the
bioavailability of the medicament and the bioavailability of the
another medicament.
[0280] In an embodiment, the medicament 190A and the another
medicament 190B are at least substantially similar instances of one
medicament. In an embodiment, the medicament and the another
medicament are at least substantially different medicaments. In an
embodiment, the first bioavailability to the animal includes a
first bioavailability characteristic and the second bioavailability
to the animal includes a second bioavailability characteristic.
[0281] In an embodiment, the release element 3230A is at least
substantially similar to the another release element 3230B. In an
embodiment, the release element is at least substantially different
from the another release element.
[0282] In an embodiment, the stimulus 190A is at least
substantially similar to the another stimulus 190B. In an
embodiment, the stimulus is at least substantially different from
the another stimulus.
[0283] In an embodiment, the final dosage form 3202 further
includes an indicator element 3280A configured to indicate an
exposure of the release element 3230A to the stimulus 192A or the
another stimulus 192B. In an embodiment, the final dosage form 3202
further includes another indicator element 3280B configured to
indicate an exposure of the another release element to the stimulus
or the another stimulus. In an embodiment, the final dosage form
further includes an indicator element, for example, indicator
element 3280A, configured to indicate an exposure of at least one
of the release element or the another release element to the
stimulus or the another stimulus.
[0284] In an embodiment, the final dosage form 3202 includes a
containment element 3240A or a containment element 3240B configured
to respectfully retain the medicament 190A or the another
medicament 190B until the final dosage form is administered to the
animal 198.
[0285] In an embodiment, the final dosage form 3202 further
includes a further dosage portion (not illustrated). The further
dosage portion includes a further chamber carrying a further
medicament. The further dosage portion also includes a further
release element in a further first medicament-release state. In the
further first medicament-release state, the further medicament has
a further first bioavailability to the animal 198 if the final
dosage form is administered to the animal in the further first
medicament-release state. The further release element is modifiable
ex vivo to a further second medicament-release state by an exposure
to a further stimulus. In the further second medicament-release
state, the further medicament has a further second bioavailability
to the animal if the final dosage form is administered to the
animal in the further second medicament-release state.
[0286] The following table illustrates several states of an example
of the final dosage form 3202:
TABLE-US-00002 TABLE 2 Example bioavailability configurations
Example Configuration #1 Example Configuration #2 Bioavailability
Profile Bioavailability Profile State of release RE 1 RE 2 RE 1 RE2
element (RE) (100 mg) (200 mg (100 mg (200 mg) TR) TR) State 1 0 0
1 0 (initial) State 2 1 0 0 0 (stimulus to RE of chamber 1) State 3
0 1 1 1 (stimulus to RE of chamber 2) State 4 1 1 0 1 (stimuli to
REs of chambers 1 & 2) 0 = medicament is substantially not
bioavailable 1 = medicament is bioavailable
[0287] FIG. 42 illustrates an example environment 3300. The
environment includes a final dosage form 3302 for administering
medicament to the animal 198. The final dosage form includes a
dosage portion, illustrated as "A" Portion, having a chamber 3320A
carrying a medicament 190A. The dosage portion includes a release
element 3330A in a medicament-retention state. The medicament is
substantially not bioavailable to the animal if the final dosage
form is administered to the animal in the first
medicament-retention state. The release element is modifiable ex
vivo to a medicament-release state by an exposure to a stimulus.
The medicament is bioavailable to the animal if the final dosage
form is administered to the animal in the medicament-release state.
The final dosage form includes another dosage portion, illustrated
as "B" Portion, having another chamber 3320B carrying another
medicament 190B. The another dosage portion includes another
release element 3330B in another medicament-retention state. The
another medicament is substantially not bioavailable to the animal
if the final dosage form is administered to the animal in the
another medicament-retention state. The another release element is
modifiable ex vivo to another medicament-release state by an
exposure to another stimulus. The another medicament is
bioavailable to the animal if the final dosage form is administered
to the animal in the another medicament-release state.
[0288] FIG. 43 illustrates an example environment 3400 that
includes a final dosage form 3405 and an operational flow 3410. The
final dosage form includes a dosage portion having a chamber
carrying a medicament. The dosage portion also includes a release
element in a first medicament-release state. The medicament has a
first bioavailability to the animal if the final dosage form is
administered to the animal in the first medicament-release state.
The release element modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus, wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal in the second
medicament-release state. The final dosage form also includes
another dosage portion having another chamber carrying another
medicament. The another dosage portion also includes another
release element in another first medicament-release state. The
another medicament has another first bioavailability to the animal
if the final dosage form is administered to the animal in the
another first medicament-release state. The another release element
modifiable ex vivo to another second medicament-release state by an
exposure to another stimulus. The another medicament has another
second bioavailability to the animal if the final dosage form is
administered to the animal in the another second medicament-release
state. In an embodiment, the final dosage form 3405 may be
substantially similar to the final dosage form 3202 described in
conjunction with FIG. 41.
[0289] After a start operation, the operational flow 3410 includes
a modification operation 3420. The modification operation includes
transforming the final dosage form 3405 into a selected
medicament-release profile by initiating an ex vivo exposure of the
release element or the another release element to a modification
stimulus respectfully selected from the stimulus and the another
stimulus. For example, the selected medicament-release profile may
include a configuration of bioavailabilities of the medicament and
the another medicament to achieve a prescribed medicament dosage.
The operational flow includes an end operation. In an embodiment,
the operational flow may be implemented using the system 2100
described in conjunction with FIG. 27.
[0290] FIG. 44 illustrates an alternative embodiment of the
operational flow 3410 of FIG. 43. The operational flow may include
at least one additional operation. The at least one additional
operation may include a treatment-order operation 3450, a
release-state selection operation 3460, or a stimulus selection
operation 3470. The treatment-order operation includes receiving a
signal indicative of a chosen medicament bioavailability of the
final dosage form 3405. In an embodiment, the treatment-order
operation may include a medicament bioavailability indicated by a
physician's prescription, a request by a person to receive the
final dosage form, or a table. In an embodiment, the
treatment-order operation may be implemented using the system 2100
described in conjunction with FIG. 21. The treatment-order
operation may include at least one additional operation. The at
least one additional operation may include an operation 3452 or an
operation 3454. The operation 3452 includes receiving a
machine-initiated signal indicative of the chosen medicament
bioavailability of the final dosage form. In an embodiment, the
operation 3452 may be implemented using the other circuit(s) 2190
to receive data or an email indicative of the chosen medicament
bioavailability of the final dosage form. The operation 3454
includes receiving a signal responsive to human-initiated
indication of the chosen medicament bioavailability of the final
dosage form. In an embodiment, the operation 3454 may be
implemented using the user interface 2195 to receive a
human-initiated input by the person 2199.
[0291] The release-state selection operation 3460 includes
selecting a medicament-release state of the release element or of
the another release element in response to the chosen
medicament-bioavailability of the final dosage form. In an
embodiment, the release-state selection operation may be
implemented using the system 2100 described in conjunction with
FIG. 21. The release-state selection operation may include at least
one additional operation, such as an operation 3462. The operation
3462 includes electronically selecting a medicament-release state
of the release element or of the another release element in
response to the selected medicament-bioavailability of the final
dosage form. The selecting a medicament-release state is based on
an electronically-stored database relating medicament-release state
and medicament-bioavailability of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-release state and medicament-bioavailability of the
final dosage form. In an embodiment, the operation 3462 may be
implemented using the release-state selection circuit 2165
described in conjunction with FIG. 21. In another embodiment, the
operation 3462 may be implemented using a combination of the
release-state selection circuit 2165, the computing device 2175,
and/or the final dosage form and stimulus exposure database 2182
described in conjunction with FIG. 21.
[0292] The stimulus selection operation 3470 includes selecting the
modification stimulus from the stimulus or the another stimulus in
response to the selected medicament-release state. In an
embodiment, the stimulus selection operation may be implemented
using the system 2100 described in conjunction with FIG. 21. The
stimulus selection operation may include at least one additional
operation, such as an operation 3472. The operation 3472 includes
electronically selecting the modification stimulus from the
stimulus or the another stimulus in response to the selected
medicament-release state, the selecting the stimulus based on an
electronically-stored database relating stimuli and
medicament-release state of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-release state of the final dosage form and stimuli. In
an embodiment, the operation 3472 may be implemented using the
stimulus selection circuit 2170 described in conjunction with FIG.
21. In another embodiment, the operation 3472 may be implemented
using a combination of the stimulus selection circuit 2170, the
computing device 2175, and/or the final dosage form and stimulus
exposure database 2182 described in conjunction with FIG. 21. The
modification operation 3420 is described in conjunction with FIG.
43.
[0293] FIG. 45 illustrates an example environment 3500. The
environment includes an article of manufacture 3501. The article of
manufacture includes a final dosage form 502 for administering
medicament to an animal. The final dosage form is described in
conjunction with FIG. 5. In another embodiment, the final dosage
form 502 is substantially similar to the final dosage 3310
described in conjunction with FIG. 42.
[0294] The article of manufacture 3501 also includes instructions
3570 specifying an ex vivo exposure of the release element 530A to
the stimulus 192A (not shown) of the stimulus 192, or an ex vivo
exposure of the another release element 530B to the another
stimulus 192B (not shown) of the stimulus 190. The instructions
when implemented transform the release element to the second
medicament-release state or the another release element to the
another second medicament-release state. In an embodiment, the
instructions may be implemented using the system 2100 described in
conjunction with FIG. 27.
[0295] FIG. 46 illustrates an example article of manufacture 3602
for administering medicament to an animal. The article of
manufacture includes a first portion 3610 and a second portion
3650. The first portion includes means 3620 for carrying a
medicament 190A. In an embodiment, the means 3620 includes means
for releasably holding a medicament. The first portion also
includes means 3624 for medicament release control in a first state
wherein the medicament has a first bioavailability to the animal if
the article of manufacture is administered to the animal. The means
for medicament release control is modifiable ex vivo to a second
state by an exposure to a stimulus, wherein the medicament has a
second bioavailability to the animal if the article of manufacture
is administered to the animal. The first portion further includes
the medicament 190A. In an embodiment, the first portion includes
means 3628 for indicating an exposure of the means for medicament
release control to the stimulus.
[0296] The second portion 3650 includes another means 3660 for
carrying another medicament 190B. The second portion also includes
another means 3664 for medicament release control in another first
state wherein the another medicament has another first
bioavailability to the animal if the article of manufacture is
administered to the animal. The another means for medicament
release control is modifiable ex vivo to another second state by an
exposure to another stimulus, wherein the another medicament has
another second bioavailability to the animal if the article of
manufacture is administered to the animal. The second portion
further includes the another medicament. In an embodiment, the
second portion includes another means 3668 for indicating an
exposure of the another means for medicament release control to the
another stimulus.
[0297] FIG. 47 illustrates an environment 3700. The environment
includes a final dosage form 3702 for administering medicament to
the animal 198. The final dosage form includes a dosage portion,
illustrated as "A Dosage Portion." The dosage portion includes a
medicament 190A. The dosage portion also include a release element
3730A in a first medicament-release state wherein the medicament
has a first bioavailability to the animal if the final dosage form
is administered to the animal in the first medicament-release
state. The release element is modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus, wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal in the second
medicament-release state.
[0298] The final dosage form 3702 also includes another dosage
portion, illustrated as "Another Dosage Portion." The another
dosage portion includes a medicament 190B. The another dosage
portion also includes another release element 3730B in another
first medicament-release state wherein the another medicament has
another first bioavailability to the animal if the final dosage
form is administered to the animal in the another first
medicament-release state. The another release element is modifiable
ex vivo to another second medicament-release state by an exposure
to another stimulus, wherein the another medicament has another
second bioavailability to the animal if the final dosage form is
administered to the animal in the another second medicament-release
state.
[0299] In an embodiment, the first medicament-release state wherein
the medicament has a first bioavailability to the animal includes a
first medicament-release state wherein the medicament is not
bioavailable to the animal. In an embodiment, the first
medicament-release state wherein the medicament has a first
bioavailability to the animal includes a first medicament-release
state wherein the medicament is bioavailable to the animal. In an
embodiment, the second medicament-release state wherein the
medicament has a second bioavailability to the animal includes a
second medicament-release state wherein the medicament is not
bioavailable to the animal. In an embodiment, the second
medicament-release state wherein the medicament has a second
bioavailability to the animal includes a second medicament-release
state wherein the medicament is bioavailable to the animal. In an
embodiment, the first bioavailability to the animal includes a
first bioavailability characteristic and the second bioavailability
to the animal includes a second bioavailability characteristic.
[0300] In an embodiment, the another first medicament-release state
wherein the another medicament has another first bioavailability to
the animal includes another first medicament-release state wherein
the another medicament is not bioavailable to the animal. In an
embodiment, the another first medicament-release state wherein the
another medicament has another first bioavailability to the animal
includes another first medicament-release state wherein the another
medicament is bioavailable to the animal. In an embodiment, the
another second medicament-release state wherein the another
medicament has another second bioavailability to the animal
includes another second medicament-release state wherein the
another medicament is not bioavailable to the animal. In an
embodiment, the another second medicament-release state wherein the
another medicament has another second bioavailability to the animal
includes another second medicament-release state wherein the
another medicament is bioavailable to the animal.
[0301] In an embodiment, the stimulus includes at least one of a
mechanical stimulus, a non-ionizing radiation stimulus, an ionizing
radiation stimulus, a chemical stimulus, an acoustic stimulus, an
ultrasound stimulus, a radio wave stimulus, a microwave stimulus, a
light wave stimulus, or a thermal stimulus.
[0302] FIG. 47 also illustrates another embodiment of the example
environment 3700. The environment includes a final dosage form 3702
for administering a medicament to the animal. The final dosage form
includes a dosage portion, illustrated as "A" Dosage Portion. The
dosage portion includes a medicament 190A. The dosage portion also
include a release element 3730A. The release element is in a
medicament-holding state wherein the medicament is substantially
not bioavailable to the animal if the final dosage form is
administered to the animal in the medicament-holding state. The
release element is modifiable ex vivo to a medicament-discharging
state by an exposure to a stimulus wherein the medicament is
bioavailable to the animal if the final dosage form is administered
to the animal in the medicament-discharging state.
[0303] The final dosage form 3702 also includes another dosage
portion, illustrated as "B" Dosage Portion. The another dosage
portion includes a medicament 190B. The another dosage portion also
includes another release element 3730B in another
medicament-holding state wherein the another medicament is
substantially not bioavailable to the animal if the final dosage
form is administered to the animal in the another
medicament-holding state. The another release element is modifiable
ex vivo to another medicament-discharge state by an exposure to
another stimulus wherein the another medicament is bioavailable to
the animal if the final dosage form is administered to the animal
in the another medicament-discharge state. In an embodiment, the
final dosage form 3702 further includes an outer layer 3710
carrying the dosage portion and the another dosage portion.
[0304] The following table illustrates several states of example
embodiments of the final dosage form 2610:
TABLE-US-00003 TABLE 3 Example bioavailability configurations
Example Configuration #1 Example Configuration #2 Bioavailability
Profile Bioavailability Profile State of RE 1 RE 2 RE 1 RE 2
release (100 mg) (200 mg TR) (100 mg (200 mg element Medicament
medicament (RE) A) B) State 1 0 0 0 0 (initial) State 2 1 0 1 0
(stimulus to first RE) State 3 0 1 0 1 (stimulus to second RE)
State 4 1 1 1 1 (stimuli to both REs) 0 = medicament is
substantially not bioavailable 1 = medicament is bioavailable
[0305] FIG. 48 illustrates an example environment 3800. The example
environment includes a final dosage form 3810 for administering
medicament to an animal. The final dosage form includes a dosage
portion 3804A, and is illustrated in an embodiment as including two
molecules. In another embodiment, the dosage portion may include a
large number of molecules. A molecule of the dosage portion
includes a release element; the molecule is generally illustrated
as including a release element 3802 having a medicament (not
shown). In an embodiment, a small molecule includes the release
element. In an embodiment, a particle or polymer material includes
the release element. In an embodiment, an intelligent molecule
includes the release element. In an embodiment, a gel, illustrated
as a hydrogel 3802A, includes the release element having an
associated medicament 190A. In an embodiment, a liposome,
illustrated as a liposome 3802B, includes the release element
having an associated medicament 190B. In an embodiment, a
nanoparticle includes the release element, illustrated as a
nanosphere 3802C having an associated medicament 190C.
[0306] The release element 3802 is in a first medicament-release
state wherein the medicament has a first bioavailability to the
animal 198 if the final dosage form is administered to the animal
in the first medicament-release state. The release element is
modifiable ex vivo to a second medicament-release state by an
exposure to a stimulus, wherein the medicament has a second
bioavailability to the animal if the final dosage form is
administered to the animal in the second medicament-release
state.
[0307] The final dosage form also includes another dosage portion,
illustrated as a dosage portion 3804B, illustrated in an embodiment
as including two molecules. In another embodiment, the another
dosage portion may include a large number of molecules. A molecule
of the another dosage portion includes another release element,
generally also illustrated as release element 3802 having another
medicament (not shown). In an embodiment, another small molecule
includes the another release element. In an embodiment, another
particle or polymer material includes the another release element.
In an embodiment, another intelligent molecule includes the another
release element. In an embodiment, another gel, illustrated as the
hydrogel 3802A, includes the another release element having an
associated medicament 190A. In an embodiment, another liposome,
illustrated as the liposome 3802B, includes the another release
element having an associated medicament 190B. In an embodiment,
another nanoparticle, illustrated as the nanosphere 3802C, includes
the another release element having an associated medicament
190C.
[0308] The another release element is in another first
medicament-release state wherein the another medicament has another
first bioavailability to the animal if the final dosage form is
administered to the animal in the another first medicament-release
state. The another release element is modifiable ex vivo to another
second medicament-release state by an exposure to another stimulus,
wherein the another medicament has another second bioavailability
to the animal if the final dosage form is administered to the
animal in the another second medicament-release state.
[0309] While FIG. 48 illustrates the molecules comprising release
elements dosage portion 3804A in a proximity, in an embodiment, the
molecules comprising release elements dosage portion 3804A may be
distributed in any manner throughout the final dosage form 3810.
Likewise, in an embodiment, the molecules comprising release
elements dosage portion 3804B may be distributed in any manner
throughout the final dosage form 3810. Further, the molecules
comprising release elements dosage portion 3804A and the molecules
comprising release elements dosage portion 3804B may be
intermingled in any manner throughout the final dosage form 3810.
In an embodiment, the molecules that comprise the dosage portion
3804A and 3804B may be substantially a same type of molecule, or
may be substantially different types of molecules.
[0310] FIG. 48 also illustrates another embodiment of the example
environment 3800. The another embodiment of the example environment
includes a final dosage form 3810 for administering medicament to
an animal. The final dosage form includes a dosage portion 3804A,
illustrated in an embodiment as including two molecules. A molecule
of the dosage portion includes a release element, generally
illustrated as release element 3802, having a medicament (not
shown). In an embodiment, a small molecule includes the release
element. In an embodiment, a particle or polymer material includes
the release element. In an embodiment, an intelligent molecule
includes the release element. In an embodiment, a gel, illustrated
as a hydrogel 3802A, includes the release element having a
medicament 190A. In an embodiment, a liposome, illustrated as a
liposome 3802B, includes the release element having a medicament
190B. In an embodiment, a nanoparticle includes the release
element, illustrated as a nanosphere 2202C having a medicament
190C.
[0311] The release element 3802 is in a medicament-holding state
wherein the medicament is substantially not bioavailable to the
animal 198 if the final dosage form 3810 is administered to the
animal in the medicament-holding state. The release element is
modifiable ex vivo to a medicament-discharging state by an exposure
to a stimulus wherein the medicament is bioavailable to the animal
if the final dosage form is administered to the animal in the
medicament-discharging state.
[0312] The final dosage form also includes another dosage portion
3804B, illustrated in an embodiment, as including two molecules. A
molecule of the another dosage portion includes another release
element, generally also illustrated as release element 3802 having
another medicament (not shown). In an embodiment, another small
molecule includes the another release element. In an embodiment,
another particle or polymer material includes the another release
element. In an embodiment, another intelligent molecule includes
the another release element. In an embodiment, another gel,
illustrated as the hydrogel 3802A, includes the another release
element having a medicament 190A. In an embodiment, another
liposome, illustrated as the liposome 3802B, includes the another
release element having a medicament 190B. In an embodiment, another
nanoparticle, illustrated as the nanosphere 3802C, includes the
another release element having a medicament 190C.
[0313] The another release element is in another medicament-holding
state wherein the another medicament is substantially not
bioavailable to the animal 198 if the final dosage form 3810 is
administered to the animal in the another medicament-holding state.
The another release element is modifiable ex vivo to another
medicament-discharge state by an exposure to another stimulus
wherein the another medicament is bioavailable to the animal if the
final dosage form is administered to the animal in the another
medicament-discharge state.
[0314] FIG. 49 illustrates an example environment 3900 that
includes a final dosage form 3905 and an operational flow 3910. The
final dosage form includes a dosage portion having a medicament.
The dosage portion includes a release element in a first
medicament-release state wherein the medicament has a first
bioavailability to the animal if the final dosage form is
administered to the animal in the first medicament-release state.
The release element is modifiable ex vivo to a second
medicament-release state by an exposure to a stimulus, wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal in the second
medicament-release state. The final dosage form also includes
another dosage portion having another medicament. The another
dosage portion includes another release element in another first
medicament-release state wherein the another medicament has another
first bioavailability to the animal if the final dosage form is
administered to the animal in the another first medicament-release
state. The another release element is modifiable ex vivo to another
second medicament-release state by an exposure to another stimulus,
wherein the another medicament has another second bioavailability
to the animal if the final dosage form is administered to the
animal in the another second medicament-release state. In an
embodiment, the final dosage form 3905 is substantially similar to
the final dosage form 3702 described in conjunction with FIG. 47,
or the final dosage form 3810 described in conjunction with FIG.
48.
[0315] After a start operation, the operational flow 3910 includes
a customization operation 3920. The customization operation
includes transforming the final dosage form 3905 into a selected
medicament release profile by initiating an ex vivo exposure of the
release element or the another release element to a modification
stimulus respectfully selected from the stimulus or the another
stimulus. The operational flow includes an end operation. In an
embodiment, the customization operation may include at least one
additional operation, such as the operation 3922. The operation
3922 includes transforming the final dosage form into a selected
medicament release profile by initiating an ex vivo exposure of the
release element and the another release element to the stimulus and
the another stimulus. In an embodiment, the operational flow 3910
may be implemented using the system 2100 described in conjunction
with FIG. 27.
[0316] FIG. 50 illustrates an example alternative embodiment of the
operational flow 3910 of FIG. 49. The operational flow may include
at least one additional operation. The at least one additional
operation may include a treatment-order operation 3950, a
release-state selection operation 3960, or a stimulus selection
operation 3970. The treatment-order operation includes receiving a
signal indicative of a chosen medicament bioavailability of the
final dosage form 3905. In an embodiment, the treatment-order
operation may be implemented using the system 2100 described in
conjunction with FIG. 21. The treatment-order operation may include
at least one additional operation. The at least one additional
operation may include an operation 3952 or an operation 3954. The
operation 3952 includes receiving a machine-initiated signal
indicative of the chosen medicament bioavailability of the final
dosage form. In an embodiment, the operation 3952 may be
implemented using the other circuit(s) 2190 to receive data or an
email indicative of the chosen medicament bioavailability of the
final dosage form. The operation 3954 includes receiving a signal
responsive to human-initiated indication of the chosen medicament
bioavailability of the final dosage form. In an embodiment, the
operation 3954 may be implemented using the user interface 2195 to
receive a human-initiated input by the person 2199 described in
conjunction with FIG. 27.
[0317] The release-state selection operation 3960 includes
selecting a medicament-release state of the release element or of
the another release element in response to the chosen
medicament-bioavailability of the final dosage form. In an
embodiment, the release-state selection operation may be
implemented using the system 2100 described in conjunction with
FIG. 21. The release-state selection operation may include at least
one additional operation, such as an operation 3962. The operation
3962 includes electronically selecting a medicament-release state
of the release element or of the another release element in
response to the selected medicament-bioavailability of the final
dosage form. The selecting a medicament-release state is based on
an electronically-stored database relating medicament-release state
and medicament-bioavailability of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-release state and medicament-bioavailability of the
final dosage form. In an embodiment, the operation 3962 may be
implemented using the release-state selection circuit 2165
described in conjunction with FIG. 21. In another embodiment, the
operation 3962 may be implemented using a combination of the
release-state selection circuit 2165, the computing device 2175,
and/or the final dosage form and stimulus exposure database 2182
described in conjunction with FIG. 21.
[0318] The stimulus selection operation 3970 includes selecting the
modification stimulus from the stimulus or the another stimulus in
response to the selected medicament-release state. In an
embodiment, the stimulus selection operation may be implemented
using the system 2100 described in conjunction with FIG. 21. The
stimulus selection operation may include at least one additional
operation, such as an operation 3972. The operation 3972 includes
electronically selecting the modification stimulus from the
stimulus or the another stimulus in response to the selected
medicament-release state, the selecting the stimulus based on an
electronically-stored database relating stimuli and
medicament-release state of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-release state of the final dosage form and stimuli. In
an embodiment, the operation 3972 may be implemented using the
stimulus selection circuit 2170 described in conjunction with FIG.
21. In another embodiment, the operation 3972 may be implemented
using a combination of the stimulus selection circuit 2170, the
computing device 2175, and/or the final dosage form and stimulus
exposure database 2182 described in conjunction with FIG. 21. The
modification operation 3920 is described in conjunction with FIG.
49.
[0319] FIG. 51 illustrates an example environment 4000 that
includes an article of manufacture 4001. In an embodiment, the
article of manufacture includes the final dosage form 3702
described in conjunction with FIG. 47. The article of manufacture
also includes instructions 4070. The instructions specify an ex
vivo exposure of the release element of the final dosage form to
the stimulus or an ex vivo exposure of the another release element
of the final dosage form to the another stimulus. The instructions
when implemented transform the release element to the second
medicament-release state or the another release element to the
another second medicament-release state.
[0320] FIG. 52 illustrates an example environment 4100 that
includes an article of manufacture 4101. In an embodiment, the
article of manufacture includes the final dosage form 3810
described in conjunction with FIG. 48. The article of manufacture
also includes instructions 4170. The instructions specify an ex
vivo exposure of the release element of the final dosage form to
the stimulus or an ex vivo exposure of the another release element
of the final dosage form to the another stimulus. The instructions
when implemented transform the release element to the second
medicament-release state or the another release element to the
another second medicament-release state.
[0321] FIG. 53 illustrates an example article of manufacture 4202
for administering medicament to an animal. The article includes the
medicament 190A. The article also includes means 4224 for
medicament release control in a first state wherein the medicament
has a first bioavailability to the animal if the article of
manufacture is administered to the animal. The means for medicament
release control is modifiable ex vivo to a second state by an
exposure to a stimulus, wherein the medicament has a second
bioavailability to the animal if the article of manufacture is
administered to the animal. The article includes another medicament
190B. The article also includes another means 4264 for medicament
release control in another first state wherein the another
medicament has another first bioavailability to the animal if the
article of manufacture is administered to the animal. The another
means for medicament release control is modifiable ex vivo to
another second state by an exposure to another stimulus, wherein
the another medicament has another second bioavailability to the
animal if the article of manufacture is administered to the
animal.
[0322] In an embodiment, the article 4202 includes means 4228 for
indicating an exposure of the means 4224 for medicament release
control to the stimulus 190A. In an embodiment, the article
includes another means 4268 for indicating an exposure of the
another means 4264 for medicament release control to the another
stimulus 190B. In an embodiment, the article includes means 4280
for protecting the article of manufacture against an ex vivo
environment. In an embodiment, the article includes means 4290 for
carrying the article of manufacture into the animal.
[0323] FIG. 54 illustrates an example environment 4300. The
environment includes a final dosage form 4310 for administering
medicament to the animal 198. The final dosage form includes a
dosage portion having a site and a medicament in a first
association. The dosage portion is illustrated as "A Dosage
Portion," and illustrates a molecule having a site and the
medicament (illustrated below as medicaments 190A, 190B, and 190C)
in a first association. In another embodiment, the "A Dosage
Portion" may include a large number of molecules each respectfully
having a site and an instance of the medicament in a first
association. In an embodiment, the site is provided by a gel,
illustrated as a hydrogel 4302A, and the medicament 190A is in a
first association with the site. In an embodiment, the site of the
dosage portion is provided by a liposome, illustrated as a liposome
4302B, and the medicament 190B is in a first association with the
site. In an embodiment, the site of the dosage portion is provided
by a nanoparticle, illustrated as nanosphere 4302C and the
medicament 190C is in a first association with the site. In an
embodiment, the site of the dosage portion includes an active site
of a molecule. In an embodiment, the site of the dosage portion
includes a binding site of a molecule. In an embodiment, the site
of the dosage portion includes a site of an intelligent
molecule.
[0324] In the first association, the medicament has a first
bioavailability to the animal if the final dosage form is
administered to the animal. The first association of the site and
the medicament is modifiable ex vivo to a second association of the
site and the medicament by an exposure to a stimulus, wherein the
medicament has a second bioavailability to the animal if the final
dosage form is administered to the animal.
[0325] The final dosage form 4310 includes another dosage portion
having another site and another medicament in another first
association. The another dosage portion is illustrated as "Another
Dosage Portion," and illustrates another molecule having another
site and the another medicament (illustrated below as medicaments
190A, 190B, and 190C) in another first association. In another
embodiment, the "Another Dosage Portion" may include a large number
of another molecules each respectfully having another site and an
instance of the medicament in another first association. In an
embodiment, the another site is provided by a gel, illustrated as a
hydrogel 4302A, and the medicament 190A is in a first association
with the another site. In an embodiment, the another site of the
another dosage portion is provided by a liposome, illustrated as a
liposome 4302B, and the medicament 190B is in another first
association with the another site. In an embodiment, the another
site of the another dosage portion is provided by a nanoparticle,
illustrated as nanosphere 4302C and the medicament 190C is in
another first association with the another site. In an embodiment,
the another site of the another dosage portion includes an active
site of another molecule. In an embodiment, the another site of the
another dosage portion includes another binding site of another
molecule. In an embodiment, the another site of the another dosage
portion includes another site of another intelligent molecule.
[0326] In the another first association, the another medicament has
another first bioavailability to the animal if the final dosage
form is administered to the animal. The another first association
of the another site and the another medicament is modifiable ex
vivo to another second association of the another site and the
another medicament by an exposure to another stimulus, wherein the
another medicament has another second bioavailability to the animal
if the final dosage form is administered to the animal.
[0327] In an embodiment, the dosage portion and the another dosage
portion may be in an unstructured proximity. For example, the
dosage portion and the another dosage portion may be dispersed or
suspended in a solid transport medium, a liquid transport medium, a
gel transport medium, or a solid transport medium. In another
embodiment, the dosage portion and the another dosage portion may
be in a structured relationship in a solid transport medium, a
liquid transport medium, a gel transport medium, or a solid
transport medium.
[0328] In an embodiment, the dosage portion includes a particle. In
an embodiment, the dosage portion includes a polymeric material. In
an embodiment, the another dosage portion includes another
particle. In an embodiment, the site and the medicament in a first
association includes a site of a particle or polymeric material in
a first association with the medicament. In an embodiment, the site
and the medicament in a first association includes a site of a
particle or polymeric material encapsulating the medicament and in
a first association with the medicament. In an embodiment, the site
and the medicament in a first association includes a particle or
polymeric material site that at least one of engages, retains, or
binds the medicament in a first association. In an embodiment, the
another dosage portion includes another polymeric material.
[0329] In an embodiment, the first bioavailability to the animal
198 includes the medicament is not bioavailable to the animal. In
an embodiment, the first bioavailability to the animal includes the
medicament is bioavailable to the animal. In an embodiment, the
second bioavailability to the animal includes the medicament is not
bioavailable to the animal. In an embodiment, the second
bioavailability to the animal includes the medicament is
bioavailable to the animal. In an embodiment, the another first
bioavailability to the animal includes the another medicament is
not bioavailable to the animal. In an embodiment, the another first
bioavailability to the animal includes the another medicament is
bioavailable to the animal. In an embodiment, the another second
bioavailability to the animal includes the another medicament is
not bioavailable to the animal. In an embodiment, the another
second bioavailability to the animal includes the another second
medicament is bioavailable to the animal.
[0330] In an embodiment, the first bioavailability to the animal
includes a first bioavailability characteristic and the second
bioavailability to the animal includes a second bioavailability
characteristic. In an embodiment, the another first bioavailability
to the animal includes another first bioavailability characteristic
and the another second bioavailability to the animal includes
another second bioavailability characteristic.
[0331] In an embodiment, the stimulus includes at least one of a
mechanical stimulus, a non-ionizing radiation stimulus, an ionizing
radiation stimulus, a chemical stimulus, an acoustic stimulus, an
ultrasound stimulus, a radio wave stimulus, a microwave stimulus, a
light wave stimulus, or a thermal stimulus. In an embodiment, the
another stimulus includes at least one of a mechanical stimulus, a
non-ionizing radiation stimulus, an ionizing radiation stimulus, a
chemical stimulus, an acoustic stimulus, an ultrasound stimulus, a
radio wave stimulus, a microwave stimulus, a light wave stimulus,
or a thermal stimulus.
[0332] FIG. 54 illustrates another embodiment of the final dosage
form 4130 for administering medicament to the animal 198. In this
another embodiment, in the first association of site and the
medicament, the medicament is substantially not bioavailable to the
animal 198 if the final dosage form 4130 is administered to the
animal. The first association of the site and the medicament is
modifiable ex vivo to a second association by an exposure to a
stimulus of the stimulus 192, wherein the medicament is
substantially bioavailable to the animal if the final dosage form
is administered to the animal.
[0333] In this another embodiment, in the another first association
of the another site and the another medicament, the another
medicament is substantially not bioavailable to the animal 198 if
the final dosage form 4130 is administered to the animal. The
another first association of the another site and the another
medicament is modifiable ex vivo to another second association by
an exposure to another stimulus, wherein the another medicament is
substantially bioavailable to the animal if the final dosage form
is administered to the animal.
[0334] FIG. 55 illustrates an example environment 4400 that
includes a final dosage form 4405 and an operational flow 4420. The
final dosage form 4405 is substantially similar to the final dosage
form 4310 described in conjunction with FIG. 54.
[0335] After a start operation, the operational flow includes a
customization operation 4420. The customization operation includes
transforming the final dosage form into a selected medicament
release state by initiating an ex vivo exposure of the first
association of the site and the medicament or the another first
association of the another site and the another medicament to a
modification stimulus respectfully selected from the stimulus or
the another stimulus. The operational flow includes an end
operation.
[0336] In an embodiment, the customization operation 4420 may
include at least one additional operation, such as an operation
4422. The operation 4422 includes transforming the final dosage
form into a selected medicament release state by initiating an ex
vivo exposure of the first association of the site and the
medicament and the another first association of the another site
and the another medicament to the stimulus and the another
stimulus. In an embodiment, the operational flow 4420 may be
implemented using the system 2100 described in conjunction with
FIG. 27.
[0337] FIG. 56 illustrates an alternative embodiment of the
operational flow 4420 described in FIG. 55. In an embodiment, the
operational flow may include at least one additional operation. The
at least one additional operation may include a treatment-order
operation 4450, a release-state selection operation 4460, or a
modification-stimulus selection operation 4470. The treatment-order
operation includes receiving a signal indicative of a chosen
medicament bioavailability of the final dosage form 4405. The
treatment-order operation may be implemented using the system 2100
described in conjunction with FIG. 27. In an embodiment, the
treatment-order operation may include at least one additional
operation. The at least one additional operation may include an
operation 4452 or an operation 4454. The operation 4452 includes
receiving a machine-initiated signal indicative of the chosen
medicament bioavailability of the final dosage form. In an
embodiment, the operation 4452 may be implemented using the other
circuit(s) 2190 to receive data, an email or fax indicative of the
chosen medicament bioavailability of the final dosage form. The
operation 4454 includes receiving a signal responsive to
human-initiated indication of the chosen medicament bioavailability
of the final dosage form. In an embodiment, the operation 4454 may
be implemented using the user interface 2195 of FIG. 27 to receive
a human-initiated input by the person 2199.
[0338] The release-state selection operation 4460 includes
selecting a medicament-release state of the site and the medicament
or of the another site and the another medicament in response to
the chosen medicament-bioavailability of the final dosage form. In
an embodiment, the release-state selection operation may be
implemented using the release-state selection circuit 2165 of FIG.
27. In an embodiment, the release-state selection operation may be
implemented using the release-state selection circuit 2165 and a
human 2199 initiated input entered into the user interface 2195.
The release-state selection operation may include at least one
additional operation, such as an operation 4462. The operation 4462
includes electronically selecting a medicament-release state of the
site and the medicament or of the another site and the another
medicament in response to the chosen medicament-bioavailability of
the final dosage form, the selecting a medicament-release state
based on an electronically-stored database relating
medicament-release state and medicament-bioavailability of the
final dosage form, a computer-implemented decision table, a
digitally-maintained final dosage form transformation table, or a
digital library correlating medicament-release state and
medicament-bioavailability of the final dosage form. In an
embodiment, the operation 4462 may be implemented using the
release-state selection circuit 2165. In an embodiment, the
operation 4462 may be implemented using the release-state selection
circuit, the computing device 2175, and/or the final dosage form
and stimulus exposure database 2182 (saved on the computer-readable
storage medium 2180).
[0339] The modification-stimulus selection operation 4470 includes
selecting the modification-stimulus from the stimulus or the
another stimulus in response to the selected medicament-release
state. In an embodiment, modification-stimulus selection operation
may be implemented using the stimulus selection circuit 2170
described in conjunction with FIG. 27. The modification-stimulus
selection operation may include at least one additional operation,
such as the operation 4472. The operation 4472 electronically
selecting the modification-stimulus from the stimulus or the
another stimulus in response to the selected medicament-release
state, the selecting the modification-stimulus based on an
electronically-stored database relating stimuli and
medicament-release state of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-release state of the final dosage form and stimuli. In
an embodiment, the stimulus selection circuit, the computing device
2175, and/or the final dosage form and stimulus exposure database
2182 may cooperatively implement the operation 4472.
[0340] FIG. 57 illustrates an example environment 4500. The
environment includes an article of manufacture 4501. In an
embodiment, the article of manufacture includes the final dosage
form 4310 described in conjunction with FIG. 54. The article of
manufacture includes instructions 4570 specifying an ex vivo
exposure of the first association of the site and the medicament to
the stimulus or an ex vivo exposure of the another first
association of the another site and the another medicament to the
another stimulus. The ex vivo exposure if implemented transforms
the first association of the site and the medicament to the second
association or the another first association of the another site
and the another medicament to the another second association.
[0341] FIG. 58 illustrates an example article of manufacture 4602
for administering medicament to an animal. The article includes
means 4624 for encapsulating a medicament 190A in a first
medicament-release state. In the first medicament-release state,
medicament has a first bioavailability to the animal if the article
of manufacture is administered to the animal in the first
medicament-release state. The means for encapsulating a medicament
in a first medicament-release state is modifiable ex vivo to a
second medicament-release state by an exposure to a stimulus,
wherein the medicament has a second bioavailability to the animal
if the article of manufacture is administered to the animal in the
second medicament-release state. The article of manufacture also
includes the medicament 190A.
[0342] The article of manufacture 4602 includes another means 4664
for encapsulating another medicament 190B in another first
medicament-release state. In the another first medicament-release
state, the another medicament has another first bioavailability to
the animal if the article of manufacture is administered to the
animal in the another first medicament-release state. The another
means for encapsulating another medicament is modifiable ex vivo to
another second medicament-release state by an exposure to another
stimulus, wherein the another medicament has another second
bioavailability to the animal if the article of manufacture is
administered to the animal in the another second medicament-release
state. The article of manufacture also includes the medicament
190B.
[0343] In an embodiment, the article of manufacture may include
means 4628 for indicating an exposure of the means for
encapsulating a medicament in a first medicament-release state to
the stimulus. In an embodiment, the article of manufacture may
include another means 4668 for indicating an exposure of the
another means for encapsulating another medicament in another first
medicament-release state to the another stimulus. In an embodiment,
the article of manufacture may include means 4680 for protecting
the article of manufacture against an ex vivo environment. In an
embodiment, the article of manufacture may include means 4590 for
carrying the article of manufacture into the animal.
[0344] FIG. 59 illustrates an example environment 4700. The
environment includes a final dosage form 4710 for administering
medicament to the animal 198. The final dosage form includes a
dosage portion, illustrated as "A Dosage Portion," that includes a
substance associated with a medicament (illustrated and described
below as medicaments 190A, 190B, and 190C) in a first
release-control state. In an embodiment, the "A Dosage Portion" may
include a large number of substances each respectfully associated
with an instance of the medicament in a first release-control
state.
[0345] In an embodiment, the substance includes a gel, illustrated
as a hydrogel 4702A, associated with the medicament 190A in a first
release-control state. In an embodiment, the substance includes a
liposome, illustrated as a liposome 4702B, associated with the
medicament 190B in a first release-control state. In an embodiment,
the substance includes a nanoparticle, illustrated as nanosphere
4702C associated with the medicament 190C in a first
release-control state. In an embodiment, the substance includes an
active site of a molecule associated with the medicament in a first
release-control state. In an embodiment, the substance includes a
molecule associated with the medicament in a first release-control
state. In an embodiment, the substance includes an intelligent
molecule associated with the medicament in a first release-control
state.
[0346] In the first release control state, the medicament has a
first bioavailability to the animal 198 if the final dosage form
4710 is administered to the animal. The substance associated with
the medicament in a first release-control state is modifiable ex
vivo by an exposure to a stimulus to associate with the medicament
in a second release-control state. In the second release-control
state, the medicament has a second bioavailability to the animal if
the final dosage form is administered to the animal.
[0347] The final dosage form 4710 includes another dosage portion,
illustrated as "Another Dosage Portion," that includes another
substance associated with another medicament (illustrated and
described as medicaments 190A, 190B, and 190C) in another first
release-control state. In an embodiment, the "Another Dosage
Portion" may include a large number of another substances each
respectfully associated with an instance of the another medicament
in another first release-control state.
[0348] In an embodiment, the another substance includes another
gel, illustrated as a hydrogel 4702A, associated with the another
medicament 190A in another first release-control state. In an
embodiment, the another substance includes another liposome,
illustrated as a liposome 4702B, associated with the another
medicament 190B in another first release-control state. In an
embodiment, the another substance includes another nanoparticle,
illustrated as nanosphere 4702C associated with the another
medicament 190C in another first release-control state. In an
embodiment, the another substance includes an active site of
another molecule associated with the another medicament in another
first release-control state. In an embodiment, the another
substance includes another molecule associated with the medicament
in a first release-control state. In an embodiment, the another
substance includes another intelligent molecule associated with the
another medicament in another first release-control state.
[0349] In the another first release control state, the another
medicament has another first bioavailability to the animal 198 if
the final dosage form 4710 is administered to the animal. The
another substance associated with the another medicament in a first
release-control state is modifiable ex vivo by an exposure to
another stimulus to associate with the another medicament in
another second release-control state. In the second release-control
state, the another medicament has another second bioavailability to
the animal if the final dosage form is administered to the
animal.
[0350] In an embodiment, the dosage portion and the another dosage
portion may be in an unstructured proximity, and not necessarily
physically distinct structures. For example, the dosage portion and
the another dosage portion may be dispersed or suspended in a solid
transport medium, a liquid transport medium, a gel transport
medium, or a solid transport medium. In another embodiment, the
dosage portion and the another dosage portion may be in a
structured relationship in a solid transport medium, a liquid
transport medium, a gel transport medium, or a solid transport
medium.
[0351] In an embodiment, the substance associated with the
medicament in a first release-control state includes a particle
associated with the medicament in a first release-control state. In
an embodiment, the substance associated with the medicament in a
first release-control state includes a polymeric material
associated with the medicament in a first release-control state. In
an embodiment, the substance associated with the medicament in a
first release-control state includes a small molecule associated
with the medicament in a first release-control state. In an
embodiment, the substance associated with the medicament in a first
release-control state includes an intelligent molecule associated
with the medicament in a first release-control state. In an
embodiment, the substance associated with the medicament in a first
release-control state includes an encapsulating substance
associated with the medicament in a first release-control state. In
an embodiment, the substance associated with the medicament in a
first release-control state includes a conjugating substance joined
with the medicament in a first release-control state. In an
embodiment, the substance associated with the medicament in a first
release-control state includes a binding substance bound with the
medicament in a first release-control state. In an embodiment, the
substance associated with the medicament in a first release-control
state includes a substance at least one of engaging, or retaining
the medicament in a first release-control state.
[0352] In an embodiment, the first bioavailability includes a first
bioavailability characteristic and the second bioavailability
includes a second bioavailability characteristic. In an embodiment,
the first bioavailability to the animal includes the medicament
being substantially not bioavailable to the animal. In an
embodiment, the first bioavailability to the animal includes the
medicament being substantially bioavailable to the animal. In an
embodiment, the second bioavailability to the animal includes the
medicament being substantially not bioavailable to the animal. In
an embodiment, the second bioavailability to the animal includes
the medicament being substantially bioavailable to the animal. In
an embodiment, the second bioavailability to the animal includes
the medicament being substantially bioavailable to the animal,
wherein the second bioavailability to the animal is substantially
different than the first bioavailability to the animal.
[0353] FIG. 59 also illustrates an alternative embodiment of the
example environment 4700. The alternative embodiment of environment
includes an alternative embodiment of the final dosage form 4710
for administering medicament to the animal 198. The final dosage
form includes a dosage portion, illustrated as "A Dosage Portion,"
that includes a substance associated with a medicament (illustrated
and described below as medicaments 190A, 190B, and 190C) in a first
state. In an embodiment, the "A Dosage Portion" may include a large
number of substances each respectfully associated with an instance
of the medicament in a first state.
[0354] In an embodiment, the substance includes a gel, illustrated
as a hydrogel 4702A, associated with the medicament 190A in a first
state. In an embodiment, the substance includes a liposome,
illustrated as a liposome 4702B, associated with the medicament
190B in a first state. In an embodiment, the substance includes a
nanoparticle, illustrated as nanosphere 4702C associated with the
medicament 190C in a first state. In an embodiment, the substance
includes an active site of a molecule associated with the
medicament in a first state. In an embodiment, the substance
includes a molecule associated with the medicament in a first
state. In an embodiment, the substance includes an intelligent
molecule associated with the medicament in a first state.
[0355] In the first state, the medicament has a first
bioavailability to the animal 198 if the final dosage form 4710 is
administered to the animal. The substance associated with the
medicament in a first state is modifiable ex vivo by an exposure to
a stimulus to associate with the medicament in a second state. In
the second state, the medicament has a second bioavailability to
the animal if the final dosage form is administered to the
animal.
[0356] The final dosage form 4710 includes another dosage portion,
illustrated as "Another Dosage Portion," that includes another
substance associated with another medicament (illustrated and
described as medicaments 190A, 190B, and 190C) in another first
state. In an embodiment, the "Another Dosage Portion" may include a
large number of another substances each respectfully associated
with an instance of the another medicament in another first
state.
[0357] In an embodiment, the another substance includes another
gel, illustrated as a hydrogel 4702A, associated with the another
medicament 190A in another first state. In an embodiment, the
another substance includes another liposome, illustrated as a
liposome 4702B, associated with the another medicament 190B in
another first state. In an embodiment, the another substance
includes another nanoparticle, illustrated as nanosphere 4702C
associated with the another medicament 190C in another first state.
In an embodiment, the another substance includes an active site of
another molecule associated with the another medicament in another
first state. In an embodiment, the another substance includes
another molecule associated with the medicament in a first state.
In an embodiment, the another substance includes another
intelligent molecule associated with the another medicament in
another first state.
[0358] In the another first state, the another medicament has
another first bioavailability to the animal 198 if the final dosage
form 4710 is administered to the animal. The another substance
associated with the another medicament in a first state is
modifiable ex vivo by an exposure to another stimulus to associate
with the another medicament in another second state. In the second
state, the another medicament has another second bioavailability to
the animal if the final dosage form is administered to the
animal.
[0359] FIG. 60 illustrates an example environment 4800 that
includes a final dosage form 4805 for administering medicament to
an animal and an operational flow 4820. The final dosage form
includes a medicament. The final dosage form also includes a
substance associated with the medicament in a first release-control
state. In the first release-control state, the medicament has a
first bioavailability to the animal if the final dosage form is
administered to the animal. The substance is modifiable ex vivo by
an exposure to a stimulus to associate with the medicament in a
second release-control state. In the second release-control state,
the medicament has a second bioavailability to the animal if the
final dosage form is administered to the animal. The final dosage
form also includes another medicament. The final dosage form
includes another substance associated with the another medicament
in another first release-control state. In the another first
release-control state, the another medicament has another first
bioavailability to the animal if the final dosage form is
administered to the animal. The another substance is modifiable ex
vivo by an exposure to another stimulus to associate with the
another medicament in another second release-control state, wherein
the another medicament has another second bioavailability to the
animal if the final dosage form is administered to the animal. In
an embodiment, the final dosage form 4805 is substantially similar
to the final dosage form 4710 previously described in conjunction
with FIG. 59.
[0360] After a start operation, the operational flow 4810 includes
a customization operation 4820. The customization operation
includes transforming the final dosage form 4805 into a selected
medicament release state by initiating an ex vivo exposure of the
substance associated with the medicament in a first release-control
state or an ex vivo exposure of the another substance associated
with the another medicament in another first release-control state
to a modification stimulus respectfully selected from the stimulus
or the another stimulus. The operational flow includes an end
operation. In an embodiment, the operational flow 4810 may be
implemented using the system 2100 described in conjunction with
FIG. 27.
[0361] In an alternative embodiment, the operational flow 4810 may
include at least one additional operation, such as an operation
4822. The operation 4822 includes transforming the final dosage
form into a selected medicament release state by initiating an ex
vivo exposure of the substance associated with the medicament in a
first release-control state and an ex vivo exposure of the another
substance associated with the another medicament in another first
release-control state to the stimulus and the another stimulus.
[0362] FIG. 61 illustrates an alternative embodiment of the
operational flow 4805 described in conjunction with FIG. 60. In an
embodiment, the operational flow may include at least one
additional operation. The at least one additional operation may
include a treatment-order operation 4850, a release-state selection
operation 4860, or a modification-stimulus selection operation
4870. The treatment-order operation includes receiving a signal
indicative of a chosen medicament bioavailability of the final
dosage form. The treatment-order operation may be implemented using
the system 2100 described in conjunction with FIG. 27. The
treatment-order operation may include at least one additional
operation. The at least one additional operation may include an
operation 4852 or an operation 4854. The operation 4852 includes
receiving a machine-initiated signal indicative of a chosen
medicament bioavailability of the final dosage form. In an
embodiment, the operation 4852 may be implemented using the other
circuit(s) 2190 to receive data, an email or fax indicative of the
chosen medicament bioavailability of the final dosage form. The
operation 4854 includes receiving a human-initiated a signal
indicative of a chosen medicament bioavailability of the final
dosage form. In an embodiment, the operation 4854 may be
implemented using the user interface 2195 of FIG. 27 to receive a
human-initiated input by the person 2199.
[0363] The release-state selection operation 4860 includes
selecting the medicament-release state of the substance associated
with the medicament or of the another substance associated with the
another medicament in response to the chosen
medicament-bioavailability of the final dosage form. In an
embodiment, the release-state selection operation may be
implemented using the release-state selection circuit 2165 of FIG.
27. In an embodiment, the release-state selection operation may be
implemented using the release-state selection circuit 2165 and a
human 2199 initiated input entered into the user interface 2195. In
an embodiment, the release-state selection operation may include at
least one additional operation, such as an operation 4862. The
operation 4862 includes electronically selecting the
medicament-release state of the substance associated with the
medicament or of the another substance associated with the another
medicament in response to the chosen medicament-bioavailability of
the final dosage form. The selecting a medicament-release state is
based on an electronically-stored database relating
medicament-release state and medicament-bioavailability of the
final dosage form, a computer-implemented decision table, a
digitally-maintained final dosage form transformation table, or a
digital library correlating medicament-release state and
medicament-bioavailability of the final dosage form. In an
embodiment, the operation 4862 may be implemented using the
release-state selection circuit 2165. In an embodiment, the
operation 4862 may be implemented using the release-state selection
circuit, the computing device 2175, and/or the final dosage form
and stimulus exposure database 2182 (saved on the computer-readable
storage medium 2180).
[0364] The modification-stimulus selection operation 4870 includes
selecting the modification-stimulus from the stimulus or the
another stimulus in response to the selected medicament-release
state. In an embodiment, modification-stimulus selection operation
may be implemented using the stimulus selection circuit 2170
described in conjunction with FIG. 27. The modification-stimulus
selecting operation may include at least one additional operation,
such as the operation 4872. The operation 4872 includes
electronically selecting the modification-stimulus from the
stimulus or the another stimulus in response to the selected
medicament-release state, the selecting the stimulus based on an
electronically-stored database relating stimuli and
medicament-release state of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-release state of the final dosage form and stimuli. In
an embodiment, the stimulus selection circuit, the computing device
2175, and/or the final dosage form and stimulus exposure database
2182 may cooperatively implement the operation 4872. The
customization operation 4820 is described in conjunction with FIG.
60.
[0365] FIG. 62 illustrates an example article of manufacture 4902
for administering medicament to an animal. The article of
manufacture includes the medicament 190A. The article of
manufacture also includes an intelligent molecular means 4924
associated with the medicament in a first release-control state. In
the first release-control state, the medicament has a first
bioavailability to the animal if the article of manufacture is
administered to the animal. The intelligent molecular means is
modifiable ex vivo by an exposure to a stimulus to associate with
the medicament in a second release-control state. In the second
release-control state, the medicament has a second bioavailability
to the animal if the article of manufacture is administered to the
animal.
[0366] The article of manufacture 4902 includes the another
medicament 190B. The article of manufacture also include another
intelligent molecular means 4964 associated with the another
medicament in another first release-control state. In the another
first release-control state, the another medicament has another
first bioavailability to the animal if the article of manufacture
is administered to the animal. The another intelligent molecular
means is modifiable ex vivo by an exposure to another stimulus to
associate with the another medicament in another second
release-control state. In the another second release-control state,
the another medicament has another second bioavailability to the
animal if the article of manufacture is administered to the
animal.
[0367] In an embodiment, the article of manufacture 4902 includes
means 4928 for indicating an exposure to the stimulus of the
intelligent molecular means associated with a medicament in a first
medicament-release state. In an embodiment, the article of
manufacture includes another means 4968 for indicating an exposure
to the another stimulus of the another intelligent molecular means
associated with another medicament in another first
medicament-release state. In an embodiment, the article of
manufacture includes means 4980 for protecting the article of
manufacture against an ex vivo environment. In an embodiment, the
article of manufacture includes means 4990 for carrying the article
of manufacture into the animal.
[0368] FIG. 63 illustrates an example environment 5000. The
environment includes a final dosage form 5010 for administering
medicament to the animal 198. The final dosage form includes at
least two respective instances of a medicament and a substance,
illustrated as instances 5002.
[0369] The final dosage form 5010 includes an instance 5002.1 of a
substance carrying a medicament in a first medicament-release
state. In an embodiment, the instance 5002.1 may include a large
number of substances each respectfully carrying the medicament in a
first medicament-release state. In an embodiment, the substance
includes a gel, illustrated as a hydrogel 5002A, carrying the
medicament 190A in a first medicament-release state. In an
embodiment, the substance includes a liposome, illustrated as a
liposome 5002B, carrying the medicament 190B in a first
medicament-release state. In an embodiment, the substance includes
a nanoparticle, illustrated as nanosphere 5002C carrying the
medicament 190C in a first medicament-release state. In an
embodiment, the substance includes an active site of a molecule
carrying the medicament in a first medicament-release state. In an
embodiment, the substance includes a molecule carrying the
medicament in a first medicament-release state. In an embodiment,
the substance includes an intelligent molecule carrying the
medicament in a first medicament-release state.
[0370] The medicament has a first bioavailability to the animal 198
if the final dosage form 5010 is administered to the animal. The
substance is modifiable ex vivo by an exposure to a first stimulus
to carry the medicament in a second medicament-release state. In
the second medicament-release state, the medicament has a second
bioavailability to the animal if the final dosage form is
administered to the animal. The substance is modifiable ex vivo by
an exposure to a second stimulus to carry the medicament in a third
medicament-release state. In the third medicament-release state,
the medicament has a third bioavailability to the animal if the
final dosage form is administered to the animal.
[0371] The final dosage form 5010 includes another instance 5002.2
of another substance carrying another medicament in another first
medicament-release state. In an embodiment, the another instance
5002.2 may include a large number of another substances each
respectfully carrying the another medicament in another first
medicament-release state. In an embodiment, the another substance
includes a gel, illustrated as a hydrogel 5002A, carrying the
another medicament 190A in another first medicament-release state.
In an embodiment, the another substance includes a liposome,
illustrated as a liposome 5002B, carrying the another medicament
190B in another first medicament-release state. In an embodiment,
the another substance includes another nanoparticle, illustrated as
nanosphere 5002C carrying the another medicament 190C in another
first medicament-release state. In an embodiment, the another
substance includes another active site of another molecule carrying
the another medicament in another first medicament-release state.
In an embodiment, the another substance includes another molecule
carrying the another medicament in another first medicament-release
state. In an embodiment, the another substance includes another
intelligent molecule carrying the another medicament in another
first medicament-release state.
[0372] The another medicament has another first bioavailability to
the animal if the final dosage form is administered to the animal.
The another substance is modifiable ex vivo by an exposure to
another first stimulus to carry the another medicament in another
second medicament-release state. In the another second
medicament-release state, the another medicament has another second
bioavailability to the animal if the final dosage form is
administered to the animal. The another substance is modifiable ex
vivo by an exposure to another second stimulus to carry the another
medicament in another third medicament-release state. In the
another third medicament-release state, the another medicament has
another third bioavailability to the animal if the final dosage
form is administered to the animal.
[0373] In an embodiment, the substance 5002 carrying the medicament
in a first medicament-release state includes a substance having a
modifiable medicament release characteristic and carrying the
medicament in a first medicament-release state. In an embodiment,
the substance carrying the medicament in a first medicament-release
state includes a substance carrying the medicament in an initial
medicament-retention state. In an embodiment, the substance
carrying the medicament in a first medicament-release state
includes a particle carrying the medicament in a first
medicament-release state. In an embodiment, the substance carrying
the medicament in a first medicament-release state includes a
polymeric material carrying the medicament in a first
medicament-release state. In an embodiment, the substance carrying
the medicament in a first medicament-release state includes a small
molecule carrying the medicament in a first medicament-release
state. In an embodiment, the substance carrying the medicament in a
first medicament-release state includes a capsule structure
carrying the medicament in a first medicament-release state.
[0374] In an embodiment, the medicament has a first bioavailability
to the animal includes the medicament is not bioavailable to the
animal. In an embodiment, the medicament has a first
bioavailability to the animal includes the medicament is
bioavailable to the animal. In an embodiment, the medicament has a
second bioavailability to the animal includes the medicament is not
bioavailable to the animal. In an embodiment, the medicament has a
second bioavailability to the animal includes the medicament is
bioavailable to the animal. In an embodiment, the medicament has a
third bioavailability to the animal includes the medicament is not
bioavailable to the animal. In an embodiment, the medicament has a
third bioavailability to the animal includes the medicament is
bioavailable to the animal.
[0375] In an embodiment, the another medicament has another first
bioavailability to the animal includes the another medicament is
not bioavailable to the animal. In an embodiment, the another
medicament has another first bioavailability to the animal includes
the another medicament is bioavailable to the animal. In an
embodiment, the another medicament has another second
bioavailability to the animal includes wherein the another
medicament is not bioavailable to the animal. In an embodiment, the
another medicament has another second bioavailability to the animal
includes the another medicament is bioavailable to the animal. In
an embodiment, the another medicament has another third
bioavailability to the animal includes the another medicament is
not bioavailable to the animal. In an embodiment, the another
medicament has another third bioavailability to the animal includes
the another medicament is bioavailable to the animal. In an
embodiment, the first bioavailability includes a first
bioavailability characteristic, the second bioavailability includes
a second bioavailability characteristic, and the third
bioavailability includes a third bioavailability
characteristic.
[0376] The example environment 5000 of FIG. 63 illustrates another
embodiment of the final dosage form 5010 for administering
medicament to the animal 198. The final dosage form includes at
least two instances of a medicament and a substance, illustrated as
instances 5002.
[0377] The final dosage form 5010 includes an instance 5002.1 of a
substance carrying a medicament in a medicament-retention state.
The medicament is substantially not bioavailable to the animal if
the final dosage form is administered to the animal. The substance
is modifiable ex vivo by an exposure to a first stimulus to carry
the medicament in a first medicament-release state. In the first
medicament-release state, the medicament has a first
bioavailability to the animal if the final dosage form is
administered to the animal. The substance is modifiable ex vivo by
an exposure to a second stimulus to carry the medicament in a
second medicament-release state. In the second medicament-release
state, the medicament has a second bioavailability to the animal if
the final dosage form is administered to the animal.
[0378] The final dosage form 5010 includes another instance 5002.2
of another substance carrying another medicament in another
medicament-retention state. The another medicament is substantially
not bioavailable to the animal if the final dosage form is
administered to the animal 198. The another substance is modifiable
ex vivo by an exposure to another first stimulus to carry the
another medicament in another first medicament-release state. In
the another first medicament-release state, the another medicament
has another first bioavailability to the animal if the final dosage
form is administered to the animal. The another substance is
modifiable ex vivo by an exposure to another second stimulus to
carry the another medicament in another second medicament-release
state. In the another second medicament-release state, the another
medicament has another second bioavailability to the animal if the
final dosage form is administered to the animal.
[0379] The following table illustrates several states of example
embodiments of the final dosage form 5010:
TABLE-US-00004 TABLE 4 Example bioavailability configurations
Example Configuration #1 Example Configuration #2 Bioavailability
Bioavailability State of Substance 1 Substance 2 Substance 1
Substance 2 substance (100 mg (200 mg TR (100 mg (200 mg medicament
medicament medicament medicament A) A) A) B) State 1 0 0 1 0
(initial) State 2 1 0 0 0 (first stimulus to Substance 1) State 3 2
0 2 0 (second stimulus to Substance 1) State 4 0 1 1 1 (another
first stimulus to Substance 2) State 4 0 2 1 2 (another second
stimulus to Substance 2) State 5 1 1 0 1 (first stimulus to
Substance 1, and another first stimulus to Substance 2) State 6 2 1
2 1 (second stimulus to Substance 1, and another first stimulus to
Substance 2) State 7 1 2 0 2 (first stimulus to Substance 1, and
another second stimulus to Substance 2) State 8 2 2 1 2 (second
stimulus to Substance 1, and another second stimulus to Substance
2) 0 = medicament is substantially not bioavailable 1 = medicament
is bioavailable 2 = medicament is bioavailable in a substantially
different characteristic than in bioavailability 1
[0380] FIG. 64 illustrates an example environment 5100. The
environment includes a final dosage form 5110 for administering
medicament to the animal 198. An element of the final dosage form
is illustrated as an element 5102.1. Another element of the final
dosage includes another element 5102.2 (not shown). The element and
the another element may be included in a transport medium (not
shown) of the final dosage form. The transport medium may include a
carrier, admixture, diluent, or excipient.
[0381] In an embodiment, the element 5102.1 of the final dosage
form 5110 includes an "A Dosage Portion" that is substantially
similar to final dosage form 102 described in conjunction with FIG.
1, and a "Another Dosage Portion" that is substantially similar to
final dosage form 302 described in conjunction with FIG. 3. The
element 5102.1 of the final dosage form 5110 includes a medicament,
illustrated in "A Dosage Portion" as the medicament 190A, and a
medicament, illustrated in "Another Dosage Portion" as the
medicament 190B. The element 5102.1 carries the medicament 190A in
a first medicament-release state. In the first medicament-release
state, the medicament 190A has a first bioavailability to the
animal 198 if the final dosage form is administered to the animal.
The element 5102.1 is modifiable ex vivo by an exposure to a first
stimulus to carry the medicament 190A in a second
medicament-release state. In the second medicament-release state,
the medicament 190A has a second bioavailability to the animal if
the final dosage form is administered to the animal.
[0382] The element 5102.1 carries the medicament 190B in the "B
Dosage Portion" in the first medicament-release state. In the first
medicament-release state, the medicament 190B has a first
bioavailability to the animal 198 if the final dosage form is
administered to the animal. The "Another Dosage Portion" of element
5102.1 is modifiable ex vivo by an exposure to a second stimulus to
carry the medicament 190B in a third medicament-release state. In
the third medicament-release state, the medicament has a third
bioavailability to the animal if the final dosage form is
administered to the animal.
[0383] In an embodiment, the element 5102.2 includes another
medicament having release states modifiable ex vivo in a manner
substantially similar to the element 5102.1.
[0384] FIG. 65 illustrates an example environment 5200. The
environment includes a final dosage form 5205 and an operational
flow 5220. In an embodiment, the final dosage form is substantially
similar to the final dosage form 5010 described in conjunction with
FIG. 63. In another embodiment, the final dosage form is
substantially similar to the final dosage form 5110 described in
conjunction with FIG. 64.
[0385] After a start operation, the operational flow 5210 includes
a customization operation 5220. The customization operation
includes transforming the final dosage form 5205 into a selected
medicament-release state by initiating an ex vivo exposure to a
modification stimulus of the substance carrying the medicament in a
first medicament-release state or the another substance carrying
the another medicament in another first medicament-release state.
The modification stimulus is respectfully selected from the first
stimulus or the second stimulus for the substance, or from the
another first stimulus or the another second stimulus for the
another substance. The operational flow includes an end operation.
In an embodiment, the operational flow 5210 may be implemented
using the system 2100 described in conjunction with FIG. 27.
[0386] In an embodiment, the customization operation 5220 may
include at least one additional operation, such as an operation
5222. The operation 5222 includes transforming the final dosage
form 5205 into a selected medicament-release state by initiating an
ex vivo exposure to a modification stimulus of the substance
carrying the medicament in a first medicament-release state and the
another substance carrying the another medicament in another first
medicament-release state. The modification stimulus includes a
stimulus selected from the first stimulus or the second stimulus
for the substance, and another stimulus selected from the another
first stimulus or the another second stimulus for the another
substance.
[0387] FIG. 66 illustrates an alternative embodiment of the
operational flow 5210 described in conjunction with FIG. 65. In an
embodiment, the operational flow may include at least one
additional operation. The at least one additional operation may
include a treatment-order operation 5250, a release-state selection
operation 5260, or a modification-stimulus selection operation
5270. The treatment order operation includes receiving a signal
indicative of a chosen medicament bioavailability of the final
dosage form. The treatment-order operation may be implemented using
the system 2100 described in conjunction with FIG. 27. The
treatment-order operation may include at least one additional
operation. The at least one additional operation may include an
operation 5252 or an operation 5254. The operation 5252 includes
receiving a machine-initiated signal indicative of a chosen
medicament bioavailability of the final dosage form. In an
embodiment, the operation 5252 may be implemented using the other
circuit(s) 2190 to receive data or an email or fax indicative of
the chosen medicament bioavailability of the final dosage form. The
operation 5254 includes receiving a human-initiated signal
indicative of the chosen medicament bioavailability of the final
dosage form. In an embodiment, the operation 5254 may be
implemented using the user interface 2195 of FIG. 27 to receive a
human-initiated input by the person 2199.
[0388] The release-state selection operation 5260 includes
selecting the medicament-release state of the substance or of the
another substance in response to the chosen
medicament-bioavailability of the final dosage form. In an
embodiment, the release-state selection operation may be
implemented using the release-state selection circuit 2165 of FIG.
27. In an embodiment, the release-state selection operation may be
implemented using the release-state selection circuit 2165 and a
human 2199 initiated input entered into the user interface 2195. In
an embodiment, the release-state selection operation may include at
least one additional operation, such as an operation 5262. The
operation 5262 includes electronically selecting the
medicament-release state of the substance or of the another
substance in response to the chosen medicament-bioavailability of
the final dosage form. The selecting a medicament-release state is
based on an electronically-stored database relating
medicament-release state and medicament-bioavailability of the
final dosage form, a computer-implemented decision table, a
digitally-maintained final dosage form transformation table, or a
digital library correlating medicament-release state and
medicament-bioavailability of the final dosage form. In an
embodiment, the operation 5262 may be implemented using the
release-state selection circuit 2165. In an embodiment, the
operation 5262 may be implemented using the release-state selection
circuit, the computing device 2175, and/or the final dosage form
and stimulus exposure database 2182 (saved on the computer-readable
storage medium 2180).
[0389] The modification-stimulus selection operation 5270 includes
selecting the modification-stimulus from the first stimulus, the
second stimulus, the another first stimulus or the another second
stimulus in response to the selected medicament-release state. In
an embodiment, modification-stimulus selection operation may be
implemented using the stimulus selection circuit 2170 described in
conjunction with FIG. 27. In an embodiment, the stimulus selection
circuit, the computing device 2175, and/or the final dosage form
and stimulus exposure database 2182 may cooperatively implement the
operation 5270. The modification-stimulus selecting operation may
include at least one additional operation, such as the operation
5272. The operation 5272 includes electronically selecting the
modification stimulus in response to the selected
medicament-release state. The selecting the modification stimulus
is based on an electronically-stored database relating stimuli and
medicament-release state of the final dosage form, a
computer-implemented decision table, a digitally-maintained final
dosage form transformation table, or a digital library correlating
medicament-release state of the final dosage form and stimuli. The
customization operation 5220 is described in conjunction with FIG.
65.
[0390] FIG. 67 illustrates an example article of manufacture 5702
for administering medicament to an animal. The article of
manufacture includes a medicament 190A. The article of manufacture
also includes intelligent molecular 5724 means associated with the
medicament in a first medicament-release state wherein the
medicament has a first bioavailability to the animal if the article
of manufacture is administered to the animal. The intelligent
molecular means is modifiable ex vivo by an exposure to a first
stimulus to carry the medicament in a second medicament-release
state. In the second medicament-release state, the medicament has a
second bioavailability to the animal if the article of manufacture
is administered to the animal. The intelligent molecular means is
modifiable ex vivo by an exposure to a second stimulus to carry the
medicament in a third medicament-release state. In the third
medicament-release state, the medicament has a third
bioavailability to the animal if the article of manufacture is
administered to the animal.
[0391] The article of manufacture includes another medicament 190B.
The article of manufacture also includes another intelligent
molecular means 5764 associated with the another medicament in
another first medicament-release state wherein the another
medicament has another first bioavailability to the animal if the
article of manufacture is administered to the animal. The another
intelligent molecular means is modifiable ex vivo by an exposure to
another first stimulus to carry the another medicament in another
second medicament-release state. In another second
medicament-release state, the another medicament has another second
bioavailability to the animal if the article of manufacture is
administered to the animal. The another intelligent molecular means
is modifiable ex vivo by an exposure to another second stimulus to
carry the another medicament in another third medicament-release
state. In another third medicament-release state, the another
medicament has another third bioavailability to the animal if the
article of manufacture is administered to the animal.
[0392] All references cited herein are hereby incorporated by
reference in their entirety or to the extent their subject matter
is not inconsistent herewith.
[0393] In some embodiments, "configured" includes at least one of
designed, set up, shaped, implemented, constructed, or adapted for
at least one of a particular purpose, application, or function.
[0394] It will be understood that, in general, terms used herein,
and especially in the appended claims, are generally intended as
"open" terms (e.g., the term "including" should be interpreted as
"including but not limited to," the term "having" should be
interpreted as "having at least," the term "includes" should be
interpreted as "includes but is not limited to," etc.). It will be
further understood that if a specific number of an introduced claim
recitation is intended, such an intent will be explicitly recited
in the claim, and in the absence of such recitation no such intent
is present. For example, as an aid to understanding, the following
appended claims may contain usage of introductory phrases such as
"at least one" or "one or more" to introduce claim recitations.
However, the use of such phrases should not be construed to imply
that the introduction of a claim recitation by the indefinite
articles "a" or "an" limits any particular claim containing such
introduced claim recitation to inventions containing only one such
recitation, even when the same claim includes the introductory
phrases "one or more" or "at least one" and indefinite articles
such as "a" or "an" (e.g., "a receiver" should typically be
interpreted to mean "at least one receiver"); the same holds true
for the use of definite articles used to introduce claim
recitations. In addition, even if a specific number of an
introduced claim recitation is explicitly recited, it will be
recognized that such recitation should typically be interpreted to
mean at least the recited number (e.g., the bare recitation of "at
least two chambers," or "a plurality of chambers," without other
modifiers, typically means at least two chambers).
[0395] Use of "Start," "End" or "Stop" blocks in the block diagrams
is not intended to indicate a limitation on the beginning or end of
any functions in the diagram. Such flowcharts or diagrams may be
incorporated into other flowcharts or diagrams where additional
functions are performed before or after the functions shown in the
diagrams of this application.
[0396] In those instances where a phrase such as "at least one of
A, B, and C," "at least one of A, B, or C," or "an [item] selected
from the group consisting of A, B, and C," is used, in general such
a construction is intended to be disjunctive (e.g., any of these
phrases would include but not be limited to systems that have A
alone, B alone, C alone, A and B together, A and C together, B and
C together, or A, B, and C together, and may further include more
than one of A, B, or C, such as A.sub.1, A.sub.2, and C together,
A, B.sub.1, B.sub.2, C.sub.1, and C.sub.2 together, or B.sub.1 and
B.sub.2 together). It will be further understood that virtually any
disjunctive word or phrase presenting two or more alternative
terms, whether in the description, claims, or drawings, should be
understood to contemplate the possibilities of including one of the
terms, either of the terms, or both terms. For example, the phrase
"A or B" will be understood to include the possibilities of "A" or
"B" or "A and B."
[0397] The herein described aspects depict different components
contained within, or connected with, different other components. It
is to be understood that such depicted architectures are merely
examples, and that in fact many other architectures can be
implemented which achieve the same functionality. In a conceptual
sense, any arrangement of components to achieve the same
functionality is effectively "associated" such that the desired
functionality is achieved. Hence, any two components herein
combined to achieve a particular functionality can be seen as
"associated with" each other such that the desired functionality is
achieved, irrespective of architectures or intermedial components.
Likewise, any two components so associated can also be viewed as
being "operably connected," or "operably coupled," to each other to
achieve the desired functionality. Any two components capable of
being so associated can also be viewed as being "operably
couplable" to each other to achieve the desired functionality.
Specific examples of operably couplable include but are not limited
to physically mateable or physically interacting components or
wirelessly interactable or wirelessly interacting components.
[0398] With respect to the appended claims the recited operations
therein may generally be performed in any order. Also, although
various operational flows are presented in a sequence(s), it should
be understood that the various operations may be performed in other
orders than those which are illustrated, or may be performed
concurrently. Examples of such alternate orderings may include
overlapping, interleaved, interrupted, reordered, incremental,
preparatory, supplemental, simultaneous, reverse, or other variant
orderings, unless context dictates otherwise. Furthermore, terms
like "responsive to," "related to," or other past-tense adjectives
are generally not intended to exclude such variants, unless context
dictates otherwise.
[0399] While various aspects and embodiments have been disclosed
herein, the various aspects and embodiments are for purposes of
illustration and are not intended to be limiting, with the true
scope and spirit being indicated by the following claims.
* * * * *
References