U.S. patent application number 11/037737 was filed with the patent office on 2008-02-28 for sublingual drug delivery device.
This patent application is currently assigned to Biodel, Inc.. Invention is credited to Craig Brown, Roderike Pohl, Trent Poole, Erik Steiner, Solomon Steiner.
Application Number | 20080047550 11/037737 |
Document ID | / |
Family ID | 34825920 |
Filed Date | 2008-02-28 |
United States Patent
Application |
20080047550 |
Kind Code |
A2 |
Steiner; Solomon ; et
al. |
February 28, 2008 |
SUBLINGUAL DRUG DELIVERY DEVICE
Abstract
A drug delivery device that aerosolizes a dry powder formulation
so that it forms a fine coating in the oral cavity and, more
specifically in the sublingual region of the oral cavity is
described herein. In the preferred embodiment, the device contains
five main parts: (i) a compressed gas canister, (ii) a dispenser
body (also referred to herein as the main housing ), (iii) a means
for storing one or more doses of a drug formulation, (iv) a means
for releasing a dose of the drug formulation such as a gas canister
or spring piston and (v) a mouthpiece. Preferred configurations
include circular, tubular, and rectangular. The means for storing
the drug formulation may be configured to separately store one or
more materials. In one embodiment, the means for storing the active
agent is in the form of one or more drug discs, where the drug
discs contain a plurality of blister packs, each storing one dose
of the drug formulation. In another embodiment, the means for
storing the active agent is a dosage cartridge containing a single
dose of the drug formulation. In yet another embodiment, the drug
formulation is stored on a ribbon containing a plurality of blister
packs, each storing one dose of the drug formulation.
Inventors: |
Steiner; Solomon; (Mount
Kisco, NY) ; Brown; Craig; (Sherman, CT) ;
Pohl; Roderike; (Sherman, CT) ; Poole; Trent;
(South Amherst, MA) ; Steiner; Erik; (New York,
NY) |
Correspondence
Address: |
PATREA L. PABST;PABST PATENT GROUP LLP
400 COLONY SQUARE, SUITE 1200
1201 PEACHTREE STREET
ATLANTA
GA
30361
UNITED STATES
404-879-2151
404-879-2160
|
Assignee: |
Biodel, Inc.
6 Christopher Columbus Avenue
Danbury
CT
06810-7352
|
Prior
Publication: |
|
Document Identifier |
Publication Date |
|
US 20050155601 A1 |
July 21, 2005 |
|
|
Family ID: |
34825920 |
Appl. No.: |
11/037737 |
Filed: |
January 18, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60/537,266 |
Jan 16, 2004 |
|
|
|
Current U.S.
Class: |
128/200.23 ;
424/46 |
Current CPC
Class: |
A61M 15/0051 20140204;
A61M 2202/064 20130101; A61M 2205/073 20130101; A61M 15/0048
20140204; A61M 15/0028 20130101; A61M 2205/8225 20130101; A61M
11/00 20130101 |
Class at
Publication: |
128/200.23 ;
424/046 |
International
Class: |
A61L 9/04 20060101
A61L009/04; A61K 9/14 20060101 A61K009/14 |
Claims
1. A dry powder drug delivery device for administration of the drug
to the oral cavity, comprising a dispenser body housing, a
mouthpiece suitable for insertion into the oral cavity of a human
in need of treatment, drug dosage storage means for one or more
drug cartridges, drug discs, drug dose ribbons or drug blister
packs, means for opening one or more drug cartridges, drug discs,
drug dose ribbons, or blister packs, and means for dispensing a
dosage from the drug cartridge or blister pack through the
mouthpiece.
2. The drug delivery device of claim 1 further comprising means for
storing one or more doses of a drug formulation selected from the
group consisting of a drug cartridge, drug blister pack, a drug
disc, and a drug dose ribbon.
3. The device of claim 1, wherein the means for dispensing a dose
of the drug formulation is selected from the group consisting of a
gas canister and spring piston.
4. The drug delivery device of claim 1 wherein the housing has a
configuration selected from the group consisting of circular
configurations, tubular configurations, and rectangular
configurations.
5. The device of claim 1, wherein the mouthpiece assembly comprises
a duct that alters the velocity of a gas flowing through the
mouthpiece.
6. The device of claim 1 comprising a protrusion on the underside
of the mouthpiece that positions the mouthpiece at a selected
distance and angle to deliver a drug to a desired region of the
oral cavity.
7. The device of claim 1 wherein the drug storage means is a
cartridge and the cartridge comprises one or more storage chambers
rotatable about the center axis of the cartridge.
8. The device of claim 7 further comprising section dividers within
the cartridge.
9. The device of claim 7 further comprising openings in the
cartridge having coverings which are punctured by the means for
opening the drug cartridge.
10. The device of claim 1 comprising a circular dispenser body
housing.
11. The device of claim 10 further comprising a drug dose
ribbon.
12. The device of claim 11, wherein the drug dose ribbons
comprising drug dose tabs of both sides of the drug dose
ribbon.
13. The device of claim 10 comprising a mouthpiece attached to the
dispenser body, wherein the mouthpiece rotates from a closed
position suitable for storage of the device in the dispenser body
to an open position, protruding outside of the dispenser body.
14. The device of claim 1 wherein the mouthpiece contains a hollow
conduit which allows for a gas and a powdered drug formulation to
flow out of the device and into the patient's mouth, and the hollow
conduit is configured to mix, disperse, and aerosolize the powdered
drug formulation.
15. The device of claim 1 comprising a plunger arm located on top
of the dispenser housing, wherein the plunger arm comprises a
movable piece with a diameter substantially the same as the
diameter of a blister pack, wherein the piece is aligned with the
mouthpiece and at least one blister pack when placed in the drug
storage means.
16. The device of claim 15 wherein the plunger arm is connected to
a gas canister for dispensing drug from a blister pack pierced by
the movable piece.
17. The device of claim 1 comprising a circular drug disc, the disc
comprising radially aligned blister packs, wherein the disc is
rotatably mounted within the dispenser body housing.
18. The device of claim 1 comprising a main housing and peripheral
fasteners, a piston assembly, a rotary mouthpiece assembly, a
cocking mechanism assembly, a firing mechanism assembly, and a drug
dose storage magazine assembly.
19. The device of claim 18 wherein the firing mechanism assembly
loads the powder dose by breaking through a blister drug dose tab,
then moves the drug dose to a dispersion chamber, cuts-off the dose
tab from a dose tab ribbon feed, and triggers the cocking mechanism
assembly to release a compressed piston assembly spring.
20. The device of claim 18 further comprising a drug dose
ribbon.
21. A method of administering a drug to a person in need thereof
comprising providing a drug delivery device in combination with a
dry powder drug, wherein the device comprises a dispenser body
housing, a mouthpiece suitable for insertion into the oral cavity
of a human in need of treatment, drug dosage storage means for one
or more drug cartridges, drug discs, drug dose ribbons or drug
blister packs, means for opening one or more drug cartridges, drug
discs, drug dose ribbons, or blister packs, and means for
dispensing a dosage from the drug cartridge or blister pack through
the mouthpiece, and administering the dry powder drug to the oral
cavity of the person using the device.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Ser. No.
60/537,266, entitled "Sublingual Drug Delivery Device" to Solomon
S. Steiner, Craig Brown, Roderike Pohl, Trent Poole, and Erik
Steiner, filed Jan. 16, 2004.
FILED OF THE INVENTION
[0002] The present invention relates to devices for oral, buccal
and/or sublingual drug delivery.
BACKGROUND OF THE INVENTION
[0003] Absorption of any molecule, such as a nutrient or
pharmaceutical agent, from the oral cavity and more specifically
from the lingual and sub-lingual regions involves a different route
than absorption of molecules through the gastrointestinal tract.
Molecules absorbed from the stomach and small intestines of the
gastro-intestinal tract are collected in the hepatic portal
drainage system and go directly to the liver where they are exposed
to a variety of enzymes which degrade many therapeutics and
nutrients, including peptides, proteins and oligonucleotides. In
contrast, molecules absorbed from the oral, lingual and sub-lingual
regions go directly into the systemic circulation, bypassing the
hepatic portal system and avoiding initial exposure to the enzymes
in the gastrointestinal tract. The oral cavity is a far gentler
environment for many molecules, especially peptides and proteins,
compared to the harsh acidic and peptide lysing environment of the
stomach and intestines. Furthermore, the underside and base of the
tongue, as well as the base of the oral cavity beneath the tongue,
are highly variegated ad vascularized, containing capillaries close
to the surface, which presents a considerable surface area to allow
rapid absorption of a desired drug or nutrient.
[0004] For the above reasons, the oral cavity and more
specifically, the lingual and sub-lingual regions of the oral
cavity, appear to be an idea site for the delivery of many
therapeutic and nutritional molecules, including peptides and
proteins. However, while a number of drugs have been successfully
delivered by this route, there remain a number of problems with
this mode of delivery.
[0005] One problem with using the oral cavity for drug delivery is
due to a patient's automatic swallowing response. A liquid placed
in the oral cavity in amounts greater than 200 microliters (.mu.L)
will usually elicit a swallowing response, removing the drug to be
delivered from the oral cavity and subjecting it to the harsh
conditions of the stomach. As a result, most of the drug delivered
to the buccal cavity is no longer available for absorption from the
oral, lingual and sub-lingual regions. This reduces the
bioavailability of the drug.
[0006] Attempts have been made to overcome this problem by affixing
the drug to a film or other adhesive that adheres to the sublingual
space, trapping the drug next to the absorptive surface. However,
this approach presents many limitations. For example, a film or
patch utilizes only a limited amount of the potential surface area
that is available for absorption, which thereby reduces the amount
of drug that can be delivered. Additionally, the base of the tongue
is irregularly shaped and variegated and as a result standardized
patches do not readily adhere to it. Further, an individual who has
a foreign substance located under the tongue normally automatically
reacts by moving the position of the foreign substance and swallow
it.
[0007] Therefore it is an object of the invention to provide a
device for administering drugs to the oral cavity, particularly the
sub-lingual region.
[0008] It is a further object of the invention to provide improved
bioavailability for oral drug delivery.
BRIEF SUMMARY OF THE INVENTION
[0009] A drug delivery device that aerosolizes a dry powder
formulation of a therapeutic agent or nutrient and dispenses the
formulation so that it forms a fine coating in the oral cavity and,
more specifically, in the sublingual region of the oral cavity, has
been developed. In the preferred embodiments the device contains
five main parts: (i) a compressed gas canister, (ii) a dispenser
body (also referred to herein as the main housing), (iii) a means
for storing one or more doses of a drug for formulation in the
housing, (iv) a means for releasing a dose of the drug formulation
and (v) a mouthpiece. In the preferred embodiment, the mouthpiece
is configured to deliver the drug to the sublingual region of the
oral cavity. Preferred housing configurations include circular,
tubular, and rectangular. The means for storing the drug
formulation may be configured to separately store one or more
materials. In one embodiment, the means for storing the active
agent is in the form of one or more drug discs, where the drug
discs contain a plurality of blister packs, each storing one dose
of the drug formulation. In another embodiment, the means for
storing the active agent is a dosage cartridge containing a single
dose of the drug formulation. In yet another embodiment, the drug
formulation is stored on a ribbon containing a plurality of blister
packs, each storing one dose of the drug formulation. In one
embodiment, the means for releasing a dose is a gas canister. In
another embodiment, the gas canister is replaced with a piston
assembly.
[0010] The device is used to administer one or more doses by
placing the mouthpiece in the mouth and activating the means for
releasing a dose. The mouthpiece is then withdrawn from the
mouth.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] FIGS. 1A, 1B and 1C are drawings of drug dispensing device
having a tubular configuration. FIGS. 1A and 1B are plan views of
the device, showing the door to the drug storage means open and
closed, respectively. FIG. 1C is an exploded plan view of the
device.
[0012] FIGS. 2A and 2B show a side view and a plan view,
respectively, of the drug storage means used in the device
described in FIGS. 1A, 1B, and 1C.
[0013] FIGS. 3A and 3B are drawings of a drug dispensing device
having a circular configuration. FIG. 3A is a plan view of the
device. FIG. 3B is a cross-sectional view of the device.
[0014] FIG. 4 is a plan view of the gas canister used in the device
described in FIGS. 3A and 3B.
[0015] FIGS. 5A and 5B are three-dimensional drawings of the drug
delivery device. FIG. 5A shows the device when it is
fully-assembled. FIG. 5B is an exploded view of the components of
the device.
[0016] FIG. 6 is a three-dimensional drawing of the piston
assembly.
[0017] FIG. 7 is a two-dimensional drawing showing a cross-section
of the fully-assembled device.
DETAILED DESCRIPTION OF THE INVENTION
I. Drug Delivery Dispenser Device
[0018] The dispenser device is a compact, handheld dispensing
device capable of delivering drug dose quantities of aerosolized
dry powder particles to any region of the oral cavity and most
specifically to the sublingual region of the oral cavity of a
patient. The dispenser device may have any suitable shape that is
compact and can be handheld. In one embodiment the device has a
generally tubular shape. In another embodiment, the device has a
generally circular shape. In a third embodiment, the device is
generally in the shape of a rectangular box.
[0019] A. Tubular Dispenser Device
[0020] FIGS. 1A, 1B and 1C illustrate a dispenser in a
substantially tubular shape with each element in a linear
alignment. The device includes a dispenser body (10), a mouthpiece
(12), a gas canister (or other means for dispensing a single drug
dose) (14), and a drug cartridge (16). In this embodiment, the
tubular dispenser device has a diameter generally ranging from 0.25
inches 2 inches, preferably from 0.5 inches to 1.5 inches. The
length generally ranges from 2 inches to 7 inches, preferably 30
inches to 5.5 inches.
[0021] 1. Dispenser Body Housing
[0022] The dispenser body (10) is designed to hold all of the
elements of the device. The dispenser body is open at both ends.
The mouthpiece (12) connects to one end and the drug dispensing
means (14) connects to the other end. The dispenser body preferably
contains a door (18), which can be opened to insert the drug
storage means (16) and closed prior to administration of the drug
dose. In a preferred embodiment, the dispenser body includes a
means for locking the door in place so that it cannot be opened
during drug administration to a patient. Preferably the means for
locking the door uses an interlocking device. Suitable interlocking
devices include a pin, cam or latch to prevent the door from
opening. Another interlocking device contains a channel with an
area with a larger opening and an area with a smaller opening. When
the mouthpiece is rotated in one position , the door is aligned
with the smaller opening in the channel, preventing the door from
opening. When the mouthpiece is rotated into a second position, the
door is aligned with the larger opening in the channel, allowing
the door to open.
[0023] 2. Mouthpiece
[0024] The mouthpiece (12) is attached to one end of the dispenser
body (10). The mouthpiece (12) is in linear alignment with the
dispenser body (10) and is rotatable about the central axis that
runs along the length of the dispenser device. In a preferred
embodiment, rotating the mouth piece a predetermined distance (e.g.
45.degree. or 90.degree. around the central axis of the device)
around the dispenser body (10) locks the door (18) in the closed
position. In the preferred embodiment, the mouthpiece is designed
to be placed in the sublingual region of a patient's mouth.
[0025] 3. Dosage Dispensing Means
[0026] Dosage dispensing means can be any means which exerts
sufficient directed force to release a single dosage from the dose
storage means and expel it from the device to a delivery site in
the patient's mouth. Examples include a gas canister or a piston.
The gas canister (14) is generally a commercially available
canister containing compressed gas. The gas may be any
pharmaceutically acceptable inhalable gas or pharmaceutically
acceptable propellant. Examples of suitable gases include nitrogen,
carbon dioxide, nitrous oxide, and air. The gas canister contains a
valve (20). Optionally, the gas canister is placed in a canister
casing (22). The canister casing surrounds the gas canister and
connects it to the dispenser body. Suitable means for connecting
the canister casing to the dispenser body include mating elements
(24A and 24B) that protrude from the casing and mate with
complementary configured spaces in the dispenser body (10) (not
shown in figures). The mating elements may be in any suitable
shape, including spheres, squares, etc. When the gas canister is
pressed against the end of the dispenser body, the valve is
punctured, allowing the gas to flow out of the canister (10) and
into the dispenser body (10).
[0027] In another embodiment, the dispensing means is a piston
which may be manually activated or activated by releasing a catch
to allow a spring to force the piston in a desired direction.
[0028] 4. Drug Cartridge
[0029] As illustrated in FIGS. 2A and 2B, the drug cartridge (16)
contains two main parts. The bottom portion of the drug cartridge
(26) contains one or more chambers to store the powdered dosage
formulation (28). The top of the cartridge (30) is in rotatable
alignment with the bottom part (26) and is able to rotate about the
center axis of the drug cartridge. The top of the cartridge
contains one or more holes (32A and 32B) that can be aligned with
the one or more holes in the bottom portion of the cartridge (holes
not shown in figures). The top of the cartridge (30) is placed over
the bottom portion (26).
[0030] In one embodiment, the top of the cartridge (30) contains
one or more section dividers (34) which, when placed inside the
botton of the cartridge, divide the cartridge chamber (28) into two
or more chambers. In another embodiment, the bottom of the
cartridge (26) contains one or more section dividers which divide
the chamber into two or more chambers (not shown in figures). Each
chamber contains a hole at the end of the bottom portion distal to
the top of the cartridge (holes not shown in figures). Prior to
placing the cartridge in the dispenser body (10), the hole(s) at
the end distal to the top of the cartridge are covered. The
covering may be a material that is punctured upon placement in the
dispensing device or the covering may be a removable material, such
as an adhesive (e.g. tape) or metallic material. The cartridge is
filled with a unit dose of the drug formulation.
[0031] In one embodiment, the cartridge has one chamber. In another
embodiment, the cartridge contains two chambers, which can be used
to separate materials that are not stable when stored together or
to separate two drug formulations (see FIGS. 2A and 2B). In still
another embodiment, the cartridge contains three or more chambers,
which can be used to separate materials that are not stable when
stored together or to separate different drug formulations.
[0032] B. Circular Dispenser Device
[0033] FIGS. 3A and 3B illustrate a dispenser device in a
substantially circular shape. The dispenser device contains a means
for opening and closing a valve in the dosage dispensing means
canister and a means for puncturing the drug storage means such as
a blister pack to administer the medicine. In a preferred
embodiment, the means for opening and closing the valve is the same
component as the means for puncturing the blister pack. In the
preferred embodiment, the device contains a dispenser body (36), a
mouthpiece (38), a gas canister (40), a plunger arm (42), and one
or more drug discs containing blister packs (44). The circular
dispensing device has a diameter (measured across the top of the
device) generally ranging from 1 inch to 5 inches, preferably
ranging from 1.5 inches to 3 inches, most preferably 2.5 inches.
The circular dispensing device has a height (or thickness)
generally ranging from 0.5 inches to 2 inches, preferably 0.75
inches to 1.5 inches.
[0034] 1. Dispenser Body
[0035] The dispenser body (36) has an opening in the bottom (46)
suitable for the placement of the gas canister. The top of the
device contains a substantially hollow circle around the perimeter
of the device (48), with a hollow center . The hollow circle is
designed to contain one or more drug discs containing a plurality
of medical powder storage chambers spaced apart from each other in
a circumferential direction (also known as "blister packs)". In the
preferred embodiment, the hollow circle is designed to contain two
discs, where one is place on top of the other. Optionally, the
circle may contain two or more drug discs.
[0036] In a preferred embodiment, the hollow circle is covered with
a flat, circular cover containing one hole in the center, another
hole near the center, and a third hole near the perimeter of the
circle. The third hole should align substantially with the location
of one of the blister packs.
[0037] 2. Mouthpiece
[0038] The mouthpiece (38) is attached to the dispenser body (36).
In the preferred embodiment, the mouthpiece (38) rotates from a
closed position suitable for storage of the device (49) in the
dispenser body to an open position, protruding outside of the
dispenser body (FIGS. 3A and 3B show the mouthpiece in the open
position). As shown in FIGS. 3A and 3B, the mouthpiece may be
attached to a cylinder (50) to allow the mouthpiece to rotate about
the cylinder. The mouthpiece contains a hollow conduit (52) which
allows for the gas and powdered drug formulation to flow out of the
device and into the patient's mouth. In the preferred embodiment,
the hollow conduit is configured to mix, disperse, and aerosolize
the powdered drug formulation.
[0039] In the preferred embodiment, the mouthpiece is designed to
be placed in the sublingual region of a patient's mouth.
[0040] 3. Drug Dispensing Means
[0041] The drug dispensing means are the same or similar to those
discussed above. Gas canister (40) shown in FIGS. 3A and 3B is a
commercially available circular canister containing compressed gas.
The gas may be any pharmaceutically acceptable inhalable gas or
pharmaceutically acceptable propellant. One manufacturer of a
suitable gas canister is 3M. The gas canister contains a gas outlet
(54) and an outer rim (56). The gas canister also contains a valve
for releasing the gas. The valve opens when the outer rim is
pressed and closes in the absence of pressure to the outer rim.
[0042] 4. Dosage Dispensing Means
[0043] The dosage dispensing means can be as discussed above. In
one embodiment, the plunger arm (42) is located on top of the
dispenser body. In a first area proximal to the mouthpiece, the
plunger arm (42) contains at least one hollow cylinder (58) with a
diameter substantially the same as the diameter of a blister pack.
This cylinder is aligned with the mouthpiece and at least one
blister pack. Optionally, the plunger arm contains more than one
hollow cylinder proximal to the mouthpiece. This embodiment is
particularly useful to administer drug formulations from a drug
disc containing two or more radially aligned blister packs. In this
embodiment the number of hollow cylinders is preferably the same as
the number of blister packs in radial alignment.
[0044] At the opposite end of the plunger arm, in an area distal to
the mouthpiece and proximal to the center of the dispensing device,
the plunger arm contains another hollow tube (60) that connects to
the gas outlet (54). In the preferred embodiment, this cylinder has
a slightly larger diameter than the gas outlet (54) so that the gas
outlet (54) fits inside the hollow tube (60).
[0045] The plunger arm also contains a conduit (62) that connects
the hollow tube proximal to the center of the device (60) with the
hollow tube proximal to the mouthpiece (58).
[0046] In one embodiment the plunger arm acts as a lever, with the
fulcrum in the center of the device. In this embodiment, when the
plunger arm is pushed down in the area proximal to the mouthpiece,
the plunger arm is raised up in the center, pulling the gas outlet
(54) up, thereby pushing in the outer rim (58) and opening the
valve inside the gas canister (not shown in figures).
[0047] In the preferred embodiment, the plunger arm also contains a
protrusion (64). When the gas canister is placed in the dispenser
body, the gas outlet (54) aligns with the hollow tube in the center
of the dispenser body (60) and the outer rim (56) is beneath the
protrusion (64). When the gas outlet (54) is pulled up and/or the
outer rim (58) is pressed by the protrusion (64), a valve inside of
the gas canister (not shown in FIG. 4) is opened and the gas flows
out of the canister through the gas outlet (54).
[0048] The protrusion (64) has a length suitable to fit inside the
dispenser body and above the outer rim (56) and to touch the outer
rim (56) only when the plunger arm is depressed. Suitable sizes
range from 0.125 to 1 inch, preferably from 0.25 inches to 0.375
inches, most preferably up to 0.375 inches. The protrusion may have
any shape that fits within the size range, including cylinder,
oval, squares and circle. The protrusion may be hollow or
solid.
[0049] To release and administer the drug formulation, the patient
pushes the plunger arm down. This motion results in puncturing the
one or more blister packs located beneath the one or more cylinders
in the area proximal to the mouthpiece (58) and empties their
contents into the hollow tube (52) in the mouthpiece.
Simultaneously, the valve in the canister opens and the gas flows
out the canister outlet (54), through the hollow tube proximal to
the center of the dispenser device (60), through the conduit in the
plunger arm (62), through the hollow tube proximal to the
mouthpiece (58), and into the tube in the mouthpiece (52). When the
gas flows through the hollow tube proximal to the mouthpiece (58)
and into the tube in the mouthpiece (52), it pushes the drug
formulation out of the device and into the patient's mouth.
[0050] 5. Drug Discs
[0051] The dispenser device may contain one or more replaceable
drug discs. The drug discs contain a plurality of storage chambers
(also known as blister packs) arranged in a circle, preferably
along the circumference of the circle. Each of the storage chambers
is sealed by a breakable wall and holds a unit-dose of medication.
A patient gains access to the medication in a given chamber by
puncturing the breakable wall associated with the storage chamber
with the hollow cylinder proximal to the mouthpiece (58).
[0052] In another embodiment, one drug disc may contain two or more
blister packs aligned radially around the circumference of the
disc. This arrangement can also be used for two or more blister
packs that can be combined to deliver a single dose or the drug
formulation.
[0053] The one or more drug discs are rotatably mounted inside the
hollow circle on the perimeter of the dispenser body (48). In one
embodiment, each of the storage chambers contains a unit dose of
the drug formulation. Alternatively, one or more the storage cells
may be combined to administer a single dose of the drug
formulation.
[0054] C. Rectangular Dispenser Device
[0055] As shown in FIGS. 5A and 5B, the generally rectangular
dispenser device, may be a piston-containing device (66). This
device contains six core subassemblies: the main housing and
peripheral fasteners (68), the piston assembly (70), the rotary
mouthpiece assembly (72), the cocking mechanism assembly (74), the
firing mechanism assembly (76), and the drug dose storage magazine
assembly (78). The rectangular dispenser device generally has a
length (measured across the top of the device, along the cocking
mechanism, with the mouthpiece in the closed position) ranging from
1.5 inches to 6 inches, preferably 2.5 inches to 4 inches. The
rectangular dispenser device generally has a height generally
ranging from 1.5 inches to 6 inches, preferably from 2 inches to 4
inches. The rectangular dispenser device generally has a depth
generally ranging from 0.5 inches to 2 inches, preferably from 0.75
inches to 1.5 inches, most preferably up to 1 inch.
[0056] 1. The Main Housing
[0057] As shown in FIG. 5B, the main housing (68) is the central
attachment member for all of the dispensing device subassemblies
and also serves as a protective housing, and hand
orientation-operation guide. The main housing may be fabricated
from a number of materials but in the preferred embodiment from
polycarbonate material.
[0058] 2. The Piston Assembly
[0059] As shown in FIG. 6, the piston assembly (70) is a
pneumatic-charged piston assembly, which contains (i) an o-ring
(80), which is used for initial testing only, (ii) a
compression-charge spring (82), (iii) a piston-member (84), (iv) a
piston-guide bearing (86), and (v) a piston-head end cap (88). The
spring-size and spring-constant can be determined by equating the
piston-force (F.sub.p) to the spring-force (F.sub.s). The
piston-force is calculated by multiplying the piston mass (m.sub.p)
by the stroke acceleration (a.sub.s) as shown in Equation 1.
F.sub.p=m.sub.p.times.a.sub.s (Eq. 1)
[0060] The spring-force (F.sub.s) is calculated by multiplying the
displacement by the spring (d) by the spring constant (C.sub.s) as
shown in Equation 1. F.sub.s=d.times.C.sub.s (Eq. 2) By equating
the piston-force (F.sub.p) to the spring-force (F.sub.s), and then
solving for acceleration (a.sub.s) or the spring-constant
(C.sub.s), one can determine the optimum piston fluidics for the
dispensing system. The piston bore and stroke can also be
calculated for optimum drug powder aerosolization and delivery.
[0061] Optionally, the piston assembly can be substituted with a
pneumatic "gas-charged" cylindrical tank.
[0062] 3. Rotary Mouthpiece Assembly
[0063] As shown in FIGS. 5A and 7, the rotary mouthpiece assembly
(72) has a convoluted ducting design (90) that slows down the gas
velocity and converts a portion of the kinetic energy into particle
mixing energy (vortex-eddies). In the preferred embodiment, this
configuration incorporates the de-agglomeration, mixing, and
dispersion mechanics necessary for low-velocity aerosolization of
slightly cohesive, large granule, particle powders. In addition,
the mouthpiece has a spring and ball detent mechanism (92) to
positively locate it in a stowed or deployed position. The
mouthpiece is configured so that the dispersion (firing) chamber
(94) of the dispenser is covered when the mouthpiece is stowed
away. The mouthpiece can mechanically cog-forward the next loaded
drug dose tab when it is placed in the stowed position. Optionally,
the drug dose tab can be fed manually by a separate feed
mechanism.
[0064] The tab on the underside of the mouthpiece (96) is used to
position the mouthpiece at an optimum distance and an optimum angle
to deliver to a desired region of the oral cavity. When a patient
uses the device, the tab (96) is placed touching and parallel to
the two front incisor teeth of the patient's lower jaw. The
distance of tab from the distal end of mouthpiece and the angle the
mouthpiece makes with the tab is optimized to dispense a dry powder
formulation to the sub-lingual region. By adjusting the angle and
the distance of the tab from the distal end of the mouthpiece, one
can optimize delivery to any area of the oral cavity, including the
upper pallet or the back of the throat.
[0065] 4. The Cocking Mechanism Assembly
[0066] The cocking mechanism assembly (74) is a user-friendly
pinch-type, i.e. thumb and forefinger, or thumb-only pull-bar that
compresses the piston assembly spring (82) for pneumatic pressure,
discharge firing. The cock-bar member tracks in one linear rail
direction along the axis of the piston compression spring. If the
pneumatic piston-accumulator assembly is substituted with a
pre-charged component, the cocking mechanism assembly can
alternatively be used as a gas cylinder loading and locking
member.
[0067] 5. Firing Mechanism Assembly
[0068] The firing mechanism assembly (76) is a complex
agglomeration of inter-connecting parts. This mechanism loads the
powder dose by breaking through the blister dose tab, then moves
the powder dose to the dispersion or "firing chamber", cuts-off the
dose tab from the dose tab ribbon feed, and triggers the cocking
mechanism assembly (74) to release the compressed piston assembly
spring (82).
[0069] 6. Drug Dose Storage Magazine Assembly
[0070] The drug dose magazine (78) assembly is composed of the
magazine housing (98) and the drug dose ribbon with feed-leader
strip (100). The ribbon can contain a plurality of two side-by-side
dose tabs, which are simultaneously loaded and dispensed within the
same "firing chamber". Alternatively, the ribbon may contain a dose
tab on only one side of the ribbon. Thus the dispenser can deliver
one drug composition or two drug compositions (or two doses of the
same drug composition) simultaneously. Further, the ribbon can be
used to administer two parts of a drug formulation that are
unstable when stored together, but stable when stored separately.
The dose tab ribbon is slot connected so that it can be cog-fed
forward. Optionally, each tab can be cut-off by a shear blade after
use.
II. Drug Formulations
[0071] The drug formulations that are administered to a patient
using the drug dispensing device are preferably in the form of a
dry powder. The powder may consist of drug only, drug plus
surfactant or other excipient, or drug plus polymer and other
excipients. Drug particles are preferably less than 100 microns in
diameter, more preferably less than 50 microns, most preferably
less than 10 microns. These may be prepared by any standard
technology including spray drying and lyophilization and
grinding.
[0072] This form provides many advantages over other forms. By
formulating the drug as a dry powder, the long term stability or
shelf life of the drug is markedly increased. It is also easier to
sterilize/sanitize a dry powder initially and to maintain a
sanitary sterile condition over an extended period of time. Two or
more substances that would not be compatible in a liquid
formulation can be stored together compatibly as a dry powder.
[0073] One or more substances can be stored and administered using
the drug dispensing devices described herein. Thus, for two or more
substances that cannot be stored together, even as a dry powder,
they can be stored separately, in different blister packs, separate
compartments in a drug cartridge, or different tabs that are
side-by-side on the drug dose ribbon, and delivered
simultaneously.
III. Methods of Using the Devices
[0074] The drug delivery device is used to administer powdered drug
compositions to the oral cavity, and is particularly useful for
sublingual drug delivery.
[0075] A. Tubular Dispenser Device
[0076] The drug cartridge may be available as a single cartridge or
as a part of a cartridge assembly. In the preferred embodiment, the
cartridge is part of a cartridge assembly. To use the tubular
device a single drug cartridge (16) is removed from a cartridge
assembly. Then the covering is removed from the bottom of the
cartridge to open the bottom of the cartridge. The The door (18) in
the dispenser body is opened, and the cartridge is placed in the
open area of the dispenser body, with the top of the cartridge (30)
proximal to the mouthpiece and the holes in the bottom of the
cartridge proximal to the gas. Then the door (18) in the dispenser
body is closed. Next a patient rotates the mouthpiece a
predetermined distance (e.g. 45.degree. or 90.degree. around the
central axis of the device) in the clockwise or counterclockwise
direction to align the one ore more holes on the top of the
cartridge (e.g. 32A and 32B) with the one ore more holes on the
bottom of the cartridge (not shown in figures). In a preferred
embodiment, the dispenser body locks the door in the closed
position, when the mouth piece is rotated the predetermined
distance. The holes are also aligned with the mouthpiece outlet.
Then the dispenser is placed under the patient's tongue. Finally,
the gas cartridge is pressed into the end of the dispenser body
that is proximal to the cartridge. This opens the gas cartridge,
releasing the compressed gas into the dispenser body and through
the hole(s) in the drug cartridge. As the gas travels through the
drug cartridge, it aerosolizes the powdered drug formulation and
pushes it out of the drug cartridge and into the mouthpiece and
administers the contents of the cartridge into the oral cavity,
most preferably the sublingual area or buccal area. In the
preferred embodiment, all of the powdered formulation in the drug
cartridge is administered to the patient in a single dose.
[0077] The dispenser then is removed from the mouth. To remove the
empty cartridge, the dispenser body is rotated a predetermined
distance in the opposite direction, the door opened and the
cartridge removed. The door is then closed and the device stored
until the next use, preferably in the absence of drug.
[0078] B. Circular Dispenser Device
[0079] To use the circular shaped device to administer the powdered
drug formulation, first, one or more drug discs are placed inside
the hollow circle on the perimeter of the dispenser body (48) and
one or more of the blister packs are aligned with the mouthpiece.
For example, if two drug discs are used, one drug disc is placed on
top of the other and both are aligned so that one blister pack in
the first disc is directly on top of one blister pack in the second
disc and both blister packs are aligned with the mouthpiece. This
arrangement can also be used for three or more drug discs. In
another embodiment, one drug disc is used and the drug is contained
in two or more blister packs aligned radially around the
circumference of the disc. The two or more blister packs or two or
more drug discs can be combined to deliver a single dose of the
drug formulation or to administer two or more drug formulations
simultaneously.
[0080] Second, the patient presses down the plunger arm (42) to
puncture the blister pack(s) with the hollow tube(s) proximal to
the mouthpiece (58) and to release the compressed gas from the gas
canister (40).
[0081] Under these conditions, gas flow directed from the gas
canister and into the mouthpiece aerosolizes the powder and pushes
the powder contained in the one or more blister packs into the
patient's mouth, preferably into the sublingual area. In the
preferred embodiment, all of the powdered drug formulation in the
punctured blister pack(s) is delivered to the patient.
[0082] In order to reuse the device to deliver another dosage of
medication, the drug disc(s) is rotated by a predetermined angle,
and then the next blister pack is aligned with the mouthpiece.
Thus, it is possible to consecutively dose a patient with a
specified amount of medical powder by rotation of the drug disc
without removing the drug disc or replacing the gas cartridge.
[0083] C. Rectangular Dispenser Device
[0084] To use the rectangular shaped device, a patient opens the
device, places the tab (96) parallel to the two front incisor teeth
of the patient's lower jaw, so that it touches these teeth. Then
the patient pulls back the cocking mechanism to compress the piston
assembly, and when the patient is ready to administer the drug, the
patient the simply triggers the firing mechanism assembly, such as
by pushing on a pin, which results in release of the drug powder
dose tab and the release of the piston, thereby mixing the powdered
drug with the air and delivering the aerosolized drug through the
mouthpiece to the patient's oral cavity.
[0085] By delivering a dry powder aerosol to the oral cavity, it is
possible to cover a large surface area in the oral cavity, thereby
increasing absorptive surface and as a consequence increase
bioavailability. Additionally, the device can uniformly cover an
irregular and variegated surface. As a fine dry powder coating, the
drug is kept in contact with the absorptive surface for much longer
periods of time without the urge to swallow.
[0086] Unless defined otherwise, all technical and scientific terms
used herein have the same meanings as commonly understood by one of
skill in the art to which the disclosed invention belongs. Although
any methods and materials similar or equivalent to those described
herein can be used in the practice or testing of the present
invention, the preferred methods, devices, and materials are as
described. Publications cited herein and the material for which
they are cited are specifically incorporated by reference. Nothing
herein is to be construed as an admission that the invention is not
entitled to antedate such disclosure by virtue of prior invention.
Those skilled in the art will recognize, or be able to ascertain
using no more than routine experimentation, many equivalents to the
specific embodiments of the invention described herein. Such
equivalents are intended to be encompassed by the following
claims.
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