U.S. patent application number 11/494769 was filed with the patent office on 2007-01-25 for method and apparatus for dispensing inhalator medicament.
Invention is credited to Robert A. Casper, David L. Gardner, Keith A. Johnson.
Application Number | 20070017513 11/494769 |
Document ID | / |
Family ID | 26952156 |
Filed Date | 2007-01-25 |
United States Patent
Application |
20070017513 |
Kind Code |
A1 |
Casper; Robert A. ; et
al. |
January 25, 2007 |
Method and apparatus for dispensing inhalator medicament
Abstract
An apparatus and method for delivering a plurality of medication
includes providing first and second medicament on a medicament pack
in separate containers for preventing either medicament from
interfering with the stability of the other. In accordance with the
method, the medicaments are preferably delivered in a single
inhalation.
Inventors: |
Casper; Robert A.; (Sanford,
NC) ; Johnson; Keith A.; (Durham, NC) ;
Gardner; David L.; (Chapel Hill, NC) |
Correspondence
Address: |
RANDALL B. BATEMAN;BATEMAN IP LAW GROUP
8 EAST BROADWAY, SUITE 550
PO BOX 1319
SALT LAKE CITY
UT
84110
US
|
Family ID: |
26952156 |
Appl. No.: |
11/494769 |
Filed: |
July 26, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10267013 |
Oct 8, 2002 |
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11494769 |
Jul 26, 2006 |
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60344544 |
Oct 19, 2001 |
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Current U.S.
Class: |
128/203.15 |
Current CPC
Class: |
A61P 31/00 20180101;
A61M 15/0003 20140204; A61P 19/02 20180101; A61P 19/08 20180101;
A61M 15/0048 20140204; A61P 25/28 20180101; A61M 2202/064 20130101;
A61P 9/10 20180101; A61P 9/12 20180101; A61P 35/00 20180101; A61M
15/0045 20130101; B65D 81/3261 20130101; A61P 25/00 20180101; A61J
1/035 20130101; A61P 11/00 20180101; A61P 25/04 20180101 |
Class at
Publication: |
128/203.15 |
International
Class: |
A61M 15/00 20060101
A61M015/00; B65D 83/06 20060101 B65D083/06 |
Claims
1-36. (canceled)
37. An inhaler for delivering medicament, the inhaler comprising: a
first inflow channel disposable in communication with a first
medicament; a second inflow channel disposable in communication
with a second medicament; and an inhalation channel in
communication with the first inflow channel and the second inflow
channel for inhaling a first medicament and a second
medicament.
38. The inhaler of claim 37, further comprising a flap for
selectively limiting airflow between the inhalation channel and at
least one of the first inflow channel and the second inflow
channel.
39. An inhaler for delivering medicament, the inhaler comprising:
at least one airflow channel through which medicament is inhaled; a
first medicament; and a second medicament, packaged separately from
the first medicament.
40. (canceled)
41. An inhaler for delivering medicament, the inhaler comprising:
means for receiving a blister pack having at least a first blister
and a second blister; at least one inflow channel, the at least one
inflow channel being disposed in communication with a first blister
and a second blister and configured for carrying medicine from the
first blister and second blister to a user; and a lancet mechanism
configured for piercing the first blister and the second
blister.
42. The inhaler of claim 41, wherein the lancet mechanism is
configured for simultaneously piercing the first blister and the
second blister.
43. The inhaler of claim 41, wherein the lancet mechanism is
configured for piercing the first blister and second blister in a
single actuation of the lancet mechanism.
44. The inhaler of claim 41, wherein the at least one inflow
comprises a first inflow channel disposed in communication with a
first blister and a second inflow channel disposed in communication
with a second blister.
45. The inhaler of claim 44, further comprising a flap configured
for delaying air flow through the second inflow channel until a
predetermined inhalation rate has been achieved.
46. The inhaler of claim 44, wherein the first inflow channel and
the second inflow channel are connected to an inhalation
channel.
47. The inhaler of claim 46, wherein the inhalation channel is
connected to a mouthpiece.
48. The inhaler of claim 41, further comprising a blister pack, the
blister having a first blister containing a first medicine and a
second blister containing a second medicine.
49. The inhaler of claim 48, wherein the first blister is in
communication with a first inflow channel and the second blister is
in communication with a second inflow channel.
50. The inhalator of claim 48, wherein the lancet mechanism is
configured for piercing the first blister and the second blister in
a single actuation.
51. An inhaler for delivering medicine, the inhaler comprising: a
housing; a blister pack disposed within the housing, the blister
pack having a first blister having a first medicine and a second
blister having a second medicine; means for opening the first
blister and the second blister; and at least one inflow channel for
carrying the medicine to a user.
52. The inhaler of claim 51, wherein the at least one inflow
channel comprises a first inflow channel disposed in communication
with the first blister and a second inflow channel disposed in
communication with the second blister.
53. The inhaler of claim 52, further comprising a flap configured
for selectively allowing airflow through the second inflow
channel.
54. The inhaler of claim 53, wherein the flap is configured for
preventing airflow through the second inflow channel until a
predetermined inhalation rate has been achieved by a user.
55. The inhaler of claim 52, wherein the first inflow channel and
the second inflow channel are connected to an inhalation
channel.
56. The inhaler of claim 51, wherein the meand for opening the
first blister and the second blister comprises a lancet
mechanism.
57. The inhaler of claim 56, wherein the lancet mechanism is
configured for piercing the first blister and the second blister in
a single actuation.
58. The inhaler of claim 51, wherein the blister pack comprises a
first plurality of blisters containing the first medicine and a
second plurality of blisters containing the second medicine.
59. The inhaler of claim 58, wherein the first plurality of
blisters and the second plurality of blisters are disposed in an
alternating arrangement.
60. The inhaler of claim 58, wherein the first plurality of
blisters is disposed in a first circular pattern and wherein the
second plurality of blisters is disposed in a second circular
pattern.
61. The inhaler of claim 51, wherein the first blister is adjacent
the second blister.
Description
RELATED APPLICATIONS
[0001] The present application is a divisional application of U.S.
patent application Ser. No. 10/267,013, filed Oct. 8, 2002, which
claims the benefit of U.S. Provisional Patent Application Ser. No.
60/344,544, filed Oct. 19, 2001.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to a drug delivery system for
a combination of medicaments for use in inhalators for the
treatment of respiratory, systemic and topical diseases, for gene
therapy, for vaccine administration, and for administration of
antigens and adjuvants (i.e. birth control). More particularly, the
present invention relates to a drug delivery system for the use of
a combination of therapeutic agents for the treatment of
respiratory diseases, e.g., asthma of whatever type or genesis,
including intrinsic (non-allergic) and extrinsic (allergic) chronic
obstructive pulmonary, airways or lung disease (COPD, COAD or
COLD), emphysema, bronchitis, acute lung injury (ALI),
pneumoconiosis, acute respiratory distress syndrome (ARDS), cystic
fibrosis (CF), allergic rhinitis and exacerbations of airways
hyperactivity consequent to other drug therapy. Other combinations
of medicaments for use in inhalators may be used to treat systemic
or topical disorders including lung and other cancers, infectious
diseases including influenza, diabetes, immuno-compromised diseases
including acquired immune deficiency syndrome (AIDS), bone
degenerative diseases including osteoporosis, neurological
degenerative diseases, including Alzheimer's and Parkinson's
disease, pain management, cardiovascular disease, obesity,
hepatitis, dermatological diseases, arthritis, hypertension and
neurological disorders including depression.
[0004] 2. State of the Art
[0005] The majority of commercially available inhalators are used
in the treatment of respiratory disorders, e.g., asthma. Asthma is
a chronic disease that affects millions of people in the United
States, and an much larger number around the world. Asthma is
typically initiated by the inhalation of antigens (sensitive
patients) but, in some patients, there is a poorly defined
mechanism(s) resulting in asthma and which is not associated with
an antigen. Asthma is a condition characterized by inflammation and
bronchial airway constriction that obstructs the patient's ability
to breathe, resulting in wheezing, coughing and tightness of the
chest.
[0006] There are many different medications used for treating
asthma. While some patients respond sufficiently well to one type
of medication or another, it is common for moderate to severe
asthmatics to use more than one medication. Typically, a
corticosteroid, e.g., beclomethasone or its derivatives and
solvates, is used to minimize asthma symptoms by decreasing the
airway hyper-responsiveness and inflammation while a
bronchodilator, e.g., albuterol or its salt, is used to increase
lung function and reduce the incidence of bronchial constriction.
However, due to the short-acting relief provided by the
bronchodilator, i.e., the bronchodilator must be administered
frequently, e.g., 4-6 times per day, which may result in poor
patient compliance. Furthermore, the bronchodilator product is less
suitable for nocturnal asthma since it may not be effective through
the duration of normal sleep.
[0007] Traditionally, the bronchodilator and steroidal product have
been provided in separate medicament inhalators. For example, an
inhalator may be used for the corticosteroid, while a separate
inhalator is used for the bronchodilator. The use of two inhalers,
however, has been found to be disadvantageous. Specifically, a
patient using two inhalators increases the likelihood that the
patient will fail to comply with the treatment protocol or may
forget to take one of the medications.
[0008] Recently, more potent and/or longer-acting corticosteroids,
e.g., fluticasone propionate, and beta2-agonist bronchodilator
drugs, e.g., salmeterol and or its salt, have been developed. This
has led to improved patient compliance, which can reduce emergency
room visits and reduce the risks associated with nocturnal
asthma.
[0009] In 1993, Glaxo Group Ltd. was issued U.S. Pat. No. 5,270,305
for a pharmaceutical composition comprising salmeterol (a
long-acting beta2-agonist) and fluticasone propionate (steroid) as
a combined preparation for the treatment of respiratory disorders,
including the simultaneous, sequential or separate administration
by inhalation via either a metered dose inhaler (MDI) or dry powder
inhaler (DPI). This combination therapy had markedly greater
efficiency and duration of bronchodilator action than previously
known combinations. In addition, it permitted the establishment of
a twice-daily dosing regimen with consequent substantial benefits
in, for example, the treatment of asthma, particularly nocturnal
asthma.
[0010] In 1997, Astra Aktiebolag was issued U.S. Pat. No. 5,674,860
for a combination product consisting of formoterol (long-acting
beta2-agonist) and budesonide (steroid) for the treatment of mild
as well as severe asthma and other respiratory disorders, including
delivery via an MDI, DPI or nebulization. Additional patents
covering combination products for the treatment of respiratory
disease include U.S. Pat. Nos. 5,972,919, 6,030,604, and
6,183,782.
[0011] Recently, these combinations of the steroid and
bronchodilator drugs have been commercialized in dry powder
inhalers, i.e., Advair.RTM. in the Diskus.RTM. DPI, and
Symbicort.RTM. in the Turbuhaler.RTM. DPI. It has been found that
the use of the two medicaments together improved patient treatment.
Additionally, requiring a patient to use a single inhalator
increases the likelihood of patient compliance as the patient need
only remember a more limited number of medicament applications.
[0012] It is evident from the above discussion that there is often
a synergistic effect of a combination of drugs when the two drugs
are administered together. It is likewise evident from the above
discussion that the use of a single inhalator increases the
likelihood of patient compliance as the patient need only remember
a more limited number of medicament applications.
[0013] While combining medications is advantageous in some ways, it
also raises concerns. Many medicaments are disposed on a carrier,
such as lactose. While the carrier can be carefully selected to a
particular medicament, the presence of multiple medicaments or
multiple carriers may render the medicaments and/or carriers
unstable. This, in turn, places limitations on the combinations of
medicaments which can be used together. By eliminating the
interaction of medicaments during storage, however, a broad range
of medicaments can be administered substantially
simultaneously.
[0014] It is therefore an object of the present invention to
address the delivery of a combination of medicaments for the
treatment of respiratory, systemic and topical diseases from dry
powder inhalators (DPIs), such as the DPI device in U.S. Pat. No.
6,209,538 and other devices.
SUMMARY AND OBJECT OF THE INVENTION
[0015] It is an object of the present invention to provide an
improved method of inhalation drug delivery for a combination of
two or more medicaments.
[0016] It is another object of the present invention to provide
such a method for treating respiratory and systemic diseases.
[0017] It is another object of the present invention to provide an
apparatus for supplying two medicaments with a single
inhalation.
[0018] The above and other objects of the present invention are
achieved through a medicament packaging system and an inhalator for
dispensing or dispersing the medicament combination. Each
medicament formulation is prepared, filled, and sealed into
separate container elements on the medicament package. The
medicament container elements are arranged in the package so that
only a container element of each medicament formulation is
available for inhalation at one time when the package is integrated
into the inhalator. The container elements are selected from the
group such as, but not limited to, blisters, capsules, vials,
ampules, tubes, pouches, bubble packs, or bottles all with
appropriate closures. The dry powder medicament formulations
combined as described above may be delivered in a single inspired
breath either simultaneously or sequentially wherein the delivery
system is comprised of a dry powder inhalator, with or without a
"breath triggering" feature for providing control of medicament
introduction into a patient's inspired air stream. However, because
the medicaments are stored separately and are not mixed until the
point of inhalation of shortly before, the risk of deterioration of
one of the medicaments or carriers is virtually eliminated.
[0019] In accordance with one aspect of the present invention, one
or more medicaments are selected from the group of brochodilators
or prophylactic agents including, but not limited to, albuterol,
albuterol sulfate, fenoterol hydrobromide, formoterol fumarate,
metaproterenol sulfate, ipratropium bromide, tiotropium bromide,
and sodium cromoglycate.
[0020] In accordance with another aspect of the present invention,
one or more medicaments are selected from the group of steroids,
androgens and glucocorticosteroids such as, but not limited to
budesonide, beclomethasone dipropionate, fluticasone propionate,
mometasone furoate, flunisolide, triamcinalone acetonide,
dehydroepiandrosterone and it's derivatives, and ciclesonide.
[0021] In accordance with yet another aspect of the present
invention, one or more medicaments is selected from the group of
compounds used to treat respiratory disorders including, but not
limited to, synthetic or natural lung surfactant, alpha-1
antitrypsin, dornase alfa, poractant alfa, oligonucleotides,
phosphodiesterase inhibitors, mast cell stabilizers, leukotriene
antagonists, antihistamines, anti-IL4 and IL5 antagonists,
neurokinin antagonists, anti-IgE monoclonal antibodies, VLA-4
antagonists, anti-L5 monoclonal antibodies, endothelin antagonists,
tachkinin antagonists, elastase antagonists, integrin antagonists,
retinoid agonists and adenosine agonists.
[0022] In accordance with still another aspect of the present
invention, one or more medicaments is selected from the group of
compounds use to diagnose respiratory ailments such as, but not
limited to, sodium chloride and uridine 5'-triphosphate,
methylcholine, and histamine.
[0023] In accordance with yet another aspect of the present
invention, one or more medicaments are selected from the group of
compounds that are typically administered orally or parenterally
such as, but not limited to morphine and its salts, fentanyl and
its salts, sufentanil and its salts, paclitaxel, vinorelbine and
its salts, salmon calcitonin, parathyroid hormone, human growth
hormone, interferons, insulin, lamivudine zidovudine, metformin
hydrochloride, cefuroxime axetil, amoxicillin, ramipril, digoxin,
zanamivir, oseltamivir and its salts, bupropion and it's salts,
citalopram and its salts, donepezil and its salts, amiloride and it
salts, and rivastigmine and its salts.
[0024] In accordance with another aspect of the present invention,
one or more of the medicament compounds has a size range
substantially less than 10 microns.
[0025] In accordance with another aspect of the present invention,
one or more of the medicament compounds has a size range
substantially less than one micron.
[0026] In accordance with still another aspect of the present
invention, one or more of the medicaments formulations are
substantially free from a carrier or excipient.
[0027] In accordance with yet another aspect of the invention, the
medicaments are present as agglomerates in the size range of 5 to
250 microns.
[0028] In accordance with another aspect of the present invention,
one or more of the medicament formulations contain one or more
carriers such as, but not limited to, lactose, glucose, raffinose,
trehalose, mannitol, sorbitol or glycine.
[0029] In accordance with another aspect of the present invention,
one or more of the medicaments are prepared as a microsphere or
microcapsule with a suitable polymeric material so that the
particle's size is substantially less than 10 microns. Microspheres
or microcapsules could be used for immediate or sustained release
of one or more medicaments in the lung.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] The above and other objects, features and advantages of the
invention will become apparent from a consideration of the
following detailed description presented in connection with the
accompanying drawings in which:
[0031] FIG. 1A shows a side view of a medicament package formed in
accordance with the principles of the present invention;
[0032] FIG. 1B shows an end view of the medicament package of FIG.
1A;
[0033] FIG. 1C shows a side view of the medicament package of FIG.
1A disposed in a mouthpiece;
[0034] FIG. 2A shows a plan view of an inhalator made in accordance
with the principles of the present invention at the beginning of an
inhalation cycle;
[0035] FIG. 2B shows the inhalator of FIG. 2A later in the
inhalation cycle;
[0036] FIG. 3A shows a side cross-sectional view of a single
blister made in accordance with the principles of the present
invention, having two sub-blisters to isolate two different
medicaments;
[0037] FIG. 3B shows a side cross-sectional view of dual blister
made in accordance with the principles of the present
invention;
[0038] FIG. 3C shows a side cross-sectional view of the dual
blister of FIG. 3B being penetrated by a piercing unit;
[0039] FIG. 4A shows a top view of a blister pack disk formed in
accordance with the principles of the present invention;
[0040] FIG. 4B shows a side view of the blister pack disk of FIG.
4A;
[0041] FIG. 5A shows a top view of a different embodiment of a
blister pack disk in accordance with the present invention;
[0042] FIGS. 5B and 5C shows a side view and an end view of a
blister shown in FIG. 5A;
[0043] FIG. 6A shows a top view of an alternate configuration of a
blister pack disk;
[0044] FIG. 6B shows a side view of one type of blister shown in
FIG. 6A;
[0045] FIG. 6C shows a side view of another type of blister shown
in FIG. 6A;
[0046] FIG. 7 shows a top view of an alternate configuration of a
blister pack disk for two medicaments on different dosing
schedules;
[0047] FIG. 8A shows a top view of an alternate configuration of a
blister pack disk;
[0048] FIG. 8B shows a side view of the blister pack disk of FIG.
8A;
[0049] FIG. 9A shows a top view of a blister card made in
accordance with the principles of the present invention;
[0050] FIG. 9B shows a side view of a blister card of FIG. 9A;
[0051] FIG. 10A shows an exploded view of yet another blister pack
disk made in accordance with the present invention;
[0052] FIG. 10B shows the blister pack disk of FIG. 10A in an
assembled state;
[0053] FIGS. 11A and 11B show an exploded view of yet another
blister card in accordance with the present invention, and an
assembled view of the same; and
[0054] FIGS. 12A and 12B show alternate embodiment in which two
half disks are combined to form a disk having two types of
medicament.
DETAILED DESCRIPTION
[0055] The invention will now be described so as to enable one
skilled in the art to make and use the invention. It is to be
understood that the following description is only exemplary of the
principles of the present invention and should not be viewed as
narrowing the pending claims. It should further be understood that
the various embodiments and examples relate to various aspects of
the present invention, and not all embodiments need to achieve all
objects of the invention.
[0056] In accordance with the present invention, it has been found
that a relatively large number of medicaments can be combined in a
dry powder inhalation drug delivery system to treat respiratory and
systemic diseases. By placing the individual medicament powders
within separate container elements in the same package and
incorporating the package into a dry powder inhalator, with or
without a "breath triggering" feature for providing control of
medicament introduction into a patient's inspired air stream, the
individual medicaments can be delivered simultaneously or
sequentially with one inhalation by the patient, thus increasing
the likelihood of compliance to achieve improved efficacy.
Furthermore, by formulating, compounding, and filling each
medicament compound into separate container elements; the
excipients or carriers and manufacturing process can be optimized
for each medicament powder's chemical stability, physical stability
and fine particle mass following introduction into the air stream.
This enables maximization of each medicament's shelf life and
targeting to the lung.
EXAMPLE 1
[0057] A formulation of albuterol sulfate, with 99% of the
particles being less than 10 microns, is prepared with an
inhalation grade of lactose so that the ratio of albuterol base to
lactose is 2:250 weight to weight. A second formulation of
fluticasone propionate, with 99% of the particles being less than
10 microns, is prepared with an inhalation grade of lactose so that
the ratio of drug to lactose is 2:250 weight to weight. Both
formulations are packaged in different capsules with nominal fills
of 50 mg of powder. The capsules are inserted into a dry powder
inhalator and pierced. The respirable dose from a single
inspiration, as measured by cascade impaction with a 4 second pulse
at 60 L/min, is 25 micrograms and 62 micrograms for albuterol base
and fluticasone propionate, respectively.
EXAMPLE 2
[0058] A formulation of formoterol fumarate, with 99% of the
particles being less than 10 microns, is prepared with lactose,
having a median particle size of 50-60 microns, so that the ratio
of drug to lactose is 1:100 weight to weight. A second formulation
of fluticasone propionate, with 99% of the particles being less
than 10 microns, is prepared with lactose, having a median particle
size of 70-80 microns, so that the ratio of drug to lactose is
1:100 weight to weight. Both formulations are packaged in different
blisters that are incorporated on the same blister card. The
blisters are arranged on the card so that only a single blister of
each formulation is available for inhalation at one time. The
triggering for the inhalation device is timed so that the
formoterol fumarate formulation is introduced into the air stream
before the fluticasone propionate formulation.
EXAMPLE 3
[0059] A formulation of formoterol fumarate, with 99% of the
particles being less than 10 microns, is prepared with lactose,
having a median particle size of 70-80 microns, so that the ratio
of drug to lactose is 1:100 weight to weight. A second formulation
of ipratropium bromide, with 99% of the particles being less than 5
microns, is prepared with lactose, having a median particle size of
70-80 microns, so that the ratio of drug to lactose is 1:100 weight
to weight. Both formulations are packaged in separate sealed tubes
that are incorporated on the inhalator. The tubes are arranged in
the inhalator so that only a single tube of each formulation is
available for inhalation at one time. The triggering for the
inhalation device is timed so that both formulations are introduced
into the air stream simultaneously.
EXAMPLE 4
[0060] A formulation of microencapsulated (as microspheres or
microcapsules) ciclesonide, with 99% of the particles being less
than 10 microns, is prepared with lactose, having a median particle
size of 50-60 microns, so that the ratio of drug to lactose is
1:100 weight to weight. A second formulation of ipratropium
bromide, with 99% of the particles being less than 10 microns, is
prepared with trehalose, having a median particle size of 50-60
microns, so that the ratio of drug to lactose is 1:50 weight to
weight. Both formulations are packaged in different blisters that
are incorporated on the same blister card. The blisters are
arranged on the card so that only a single blister of each
formulation is available for inhalation at one time. The triggering
for the inhalation device is timed so that the ipratropium bromide
formulation is introduced into the air stream before the
ciclesonide formulation.
EXAMPLE 5
[0061] A formulation of fentanyl citrate, with 99% of the particles
being less than 5 microns, is prepared with lactose, having a
median particle size of 5 microns, so that the ratio of drug to
lactose is 50:50 weight to weight. A second formulation of
sufentanil citrate, with 99% of the particles being less than 5
microns, is prepared with lactose, having a median particle size of
70-80 microns, so that the ratio of drug to lactose is 1:100 weight
to weight. Both formulations are packaged in different blisters
that are incorporated on the same blister card. The blisters are
arranged on the card so that only a single blister of each
formulation is available for inhalation at one time. The triggering
for the inhalation device is timed so that both formulations are
introduced into the air stream simultaneously.
EXAMPLE 6
[0062] A formulation of microencapsulated ciclesonide, with 99% of
the particles being less than 10 microns, is prepared with lactose,
having a median particle size of 50-60 microns, so that the ratio
of drug to lactose is 1:100 weight to weight. A second formulation
of microencapsulated triamcinalone acetonide, with 99% of the
particles being less than 10 microns, is prepared with lactose,
having a median particle size of 50-60 microns, so that the ratio
of drug to lactose is 10:100 weight to weight. Both formulations
are packaged in different vials that are incorporated in the
inhalator. The vials are arranged in the inhalator so that only a
single vial of each formulation is available for inhalation at one
time. The triggering for the inhalation device is timed so that
both formulations are introduced into the air stream
simultaneously.
EXAMPLE 7
[0063] A formulation of paclitaxel, with 99% of the particles being
less than 10 microns, is prepared with lactose, having a median
particle size of 100-120 microns, so that the ratio of drug to
lactose is 1:100 weight to weight. A second formulation of
vinorelbine tartrate, with 99% of the particles being less than 10
microns, is prepared with lactose, having a median particle size of
50-60 microns, so that the ratio of drug to lactose is 10:100
weight to weight. Both formulations are packaged in different
blisters that are incorporated on the same blister card. The
blisters are arranged on the card so that only a single blister of
each formulation is available for inhalation at one time. The
triggering for the inhalation device is timed so that the
vinorelbine tartrate formulation is introduced into the air stream
before the paclitaxel formulation.
EXAMPLE 8
[0064] A formulation of salmon calcitonin, with 99% of the
particles being less than 10 microns, is prepared with lactose,
having a median particle size of 100-120 microns, so that the ratio
of drug to lactose is 1:100 weight to weight. A second formulation
of parathyroid hormone, with 99% of the particles being less than
10 microns, is prepared with lactose, having a median particle size
of 50-60 microns, so that the ratio of drug to lactose is 10:100
weight to weight. Both formulations are packaged in different
capsules that are incorporated in the inhalator. The capsules are
arranged in the inhalator so that only a single capsule of each
formulation is available for inhalation at one time. The triggering
for the inhalation device is timed so that the salmon calcitonin
formulation is introduced into the air stream before the
parathyroid hormone formulation.
EXAMPLE 9
[0065] A formulation of lamivudine, with 99% of the particles being
less than 10 microns, is prepared with lactose, having a median
particle size of 100-120 microns, so that the ratio of drug to
lactose is 1:100 weight to weight. A second formulation of
zidovudine, with 99% of the particles being less than 10 microns,
is prepared with lactose, having a median particle size of 50-60
microns, so that the ratio of drug to lactose is 10:100 weight to
weight. A third formulation of interferon alfa-2b, with 99% of the
particles being less than 10 microns, is prepared with lactose,
having a median particle size of 50-60 microns, so that the ratio
of drug to lactose is 10:100 weight to weight. The three
formulations are packaged in different blisters that are
incorporated on the same blister card. The blisters are arranged on
the card so that only a single blister of each formulation is
available for inhalation at one time. The triggering for the
inhalation device is timed so that both formulations are introduced
into the air stream simultaneously.
EXAMPLE 10
[0066] A formulation of insulin, with 99% of the particles being
less than 10 microns, is prepared so that the drug particles form
agglomerates or aggregates that are substantially between 10 and
200 microns. A second formulation of metformin hydrochloride, with
99% of the particles being less than 10 microns, is prepared with
raffinose, having a median particle size of 50-60 microns, so that
the ratio of drug to lactose is 10:100 weight to weight. Both
formulations are packaged in different blisters that are
incorporated on the same blister card. The blisters are arranged on
the card so that only a single blister of each formulation is
available for inhalation at one time. The triggering for the
inhalation device is timed so that both formulations are introduced
into the air stream simultaneously.
EXAMPLE 11
[0067] A formulation of cefuroxime axetil, with 99% of the
particles being less than 10 microns, is prepared with mannitol,
having a median particle size of 100-120 microns, so that the ratio
of drug to lactose is 1:100 weight to weight. A second formulation
of amoxicillin, with 99% of the particles being less than 10
microns, is prepared with glucose, having a median particle size of
50-60 microns, so that the ratio of drug to lactose is 10:100
weight to weight. Both formulations are packaged in different
blisters that are incorporated on the same blister card. The
blisters are arranged on the card so that only a single blister of
each formulation is available for inhalation at one time. The
triggering for the inhalation device is timed so that both
formulations are introduced into the air stream simultaneously.
Those skilled in the art will also appreciate, in light of the
present disclosure, that the provision of two or more antibiotics
on a blister pack would allow alternate antibiotic dosing. This, in
turn, could be used to dramatically reduce the risk of antibiotic
resistant bacteria from developing.
EXAMPLE 12
[0068] A formulation of ramipril, with 99% of the particles being
less than 10 microns, is prepared with lactose, having a median
particle size of 50-70 microns, so that the ratio of drug to
lactose is 1:100 weight to weight. A second formulation of
microencapsulated digoxin, with 99% of the particles being less
than 10 microns, is prepared with raffinose, having a median
particle size of 50-60 microns, so that the ratio of drug to
lactose is 10:100 weight to weight. Both formulations are packaged
in different blisters that are incorporated on the same blister
card. The blisters are arranged on the card so that only a single
blister of each formulation is available for inhalation at one
time. The triggering for the inhalation device is timed so that
both formulations are introduced into the air stream
simultaneously.
EXAMPLE 13
[0069] A formulation of zanamivir, with 99% of the particles being
less than 10 microns, is prepared with lactose, having a median
particle size of 50-70 microns, so that the ratio of drug to
lactose is 1:100 weight to weight. A second formulation of
oseltamivir phosphate, with 99% of the particles being less than 5
microns, is prepared so that the drug content is 100% w/w. Both
formulations are packaged in different blisters that are
incorporated on the same blister card. The blisters are arranged on
the card so that only a single blister of each formulation is
available for inhalation at one time. The triggering for the
inhalation device is timed so that the oseltamivir phosphate
formulation is introduced into the air stream before the zanamivir
formulation.
EXAMPLE 14
[0070] A formulation of zanamivir, with 99% of the particles being
less than 5 microns, is prepared with glycine, having a median
particle size of 50-70 microns, so that the ratio of drug to
lactose is 1:100 weight to weight. A second formulation of
oseltamivir phosphate, with 99% of the particles being less than 5
microns, is prepared so that the drug content is 100% w/w. Both
formulations are packaged in different blisters that are
incorporated on the same blister card. The blisters are arranged on
the card so that only a single blister of each formulation is
available for inhalation at one time. The triggering for the
inhalation device is timed so that both formulations are introduced
into the air stream simultaneously.
EXAMPLE 15
[0071] A formulation of bupropion hydrochloride, with 99% of the
particles being less than 10 microns, is prepared so that the drug
content is 100% w/w. A second formulation of citalopram
hydrobromide, with 99% of the particles being less than 5 microns,
is prepared so that the drug content is 100% w/w. Both formulations
are packaged in different blisters that are incorporated on the
same blister card. The blisters are arranged on the card so that
only a single blister of each formulation is available for
inhalation at one time. The triggering for the inhalation device is
timed so that the bupropion hydrochloride formulation is introduced
into the air stream before the citalopram hydrobromide
formulation.
EXAMPLE 16
[0072] A formulation of donepezil hydrochloride, with 99% of the
particles being less than 10 microns, is prepared with lactose,
having a median particle size of 50-60 microns, so that the ratio
of drug to lactose is 1:100 weight to weight. A second formulation
of rivastigmine tartrate, with 99% of the particles being less than
10 microns, is prepared with lactose, having a median particle size
of 70-80 microns, so that the ratio of drug to lactose is 1:100
weight to weight. Both formulations are packaged in different
blisters that are incorporated on the same blister card. The
blisters are arranged on the card so that only a single blister of
each formulation is available for inhalation at one time. The
triggering for the inhalation device is timed so that both
formulations are introduced into the air stream simultaneously.
EXAMPLE 17
[0073] A formulation of gabapentenoid with 99% of the particles
being less than 10 microns, is prepared so that the drug content is
100% by weight. A second formulation of naproxen, with 99% of
particles being less than 5 microns is prepared so that the drug
content is 100% by weight. Both formulations are packaged in
different blisters that are incorporated on the same blister card.
The blisters are arranged on the card so that only a single blister
of each formulation is available for inhalation at a time. The
triggering for the inhalation device is timed so that the
gabapentenoid is introduced into the air stream before the
naproxen.
EXAMPLE 18
[0074] A formulation of telmisartan, with 99% of the particles
being less than 10 micron, is prepared so that the drug content is
100% by weight. A second formulation of lacidipine, with 99% of the
particles being less than 5 microns, is prepared so that the drug
content is 100% by weight. Both formulations are packaged in
different blisters that are incorporated on the same blister card.
The blisters are arranged on the card so that only a single blister
of each formulation is available for inhalation at one time. The
triggering for the inhalation device is timed so that the
telmisartan is introduced into the air stream before the
lacidipine.
[0075] The medicament formulations packaged according to the
present invention can be delivered to the patient via any common
inhalator, such as those which use blister packs or dispense bulk
medicament. Furthermore, inhalers can be specially configured to
control flow rates and when the medicaments are distributed to the
user.
[0076] While the 18 examples above are typical; it should be
appreciated that any of the drugs can be formulated, filled, and
sealed in a blister package according to the present invention. The
desired ratios of active drug in the medicament formulations will
depend both on the particular medicament being used and on the
medical needs of the patient.
[0077] As indicated above, the formulation can be used in
traditional inhalators. In other words, the formulations can be
dispensed from the single dose or multiple dose blister packs to
increase the ease of use. Dose is defined as the amount of each
medicament powder delivered with a single inhalation. Additionally,
the formulations can be dispensed from a device in which the
formulations are mixed with an air stream at a specific volumetric
flow rate, thereby increasing the likelihood of deep lung targeting
of one or more of the medicaments. An example of an inhalator
providing such dispensing is discussed in U.S. Pat. No. 5,98,163.
Propellant-based formulations can be delivered through an inhalator
such as that described in U.S. Pat. No. 5,826,571 (Casper et
al.).
[0078] Turning now to the drawings, there are shown numerous
different configurations for supplying two different drugs to the
user from a single device without the risk of the medicaments or
their carriers interfering with the stability of the other.
Furthermore, while discussed for simplicity as having two drugs, it
will also be appreciated that the method of the present invention
can involve three or more drugs being inhaled though a common
inhaler.
[0079] FIGS. 1A, 1B and 1C show an embodiment wherein the
medicament, packaged in a pair of capsules 10 and 12 held in a
medicament package 14. The capsules are disposed adjacent each
other, but each capsule 10, 12 keeps the contents thereof from
interfering with the contents of the other capsule. In use, the
capsules 10, 12 are pierced or broken and the user inhales through
the mouthpiece 18, thereby receiving the appropriate dose of two
medications simultaneously.
[0080] FIG. 2A shows a plan view of an inhalator made in accordance
with the principles of the present invention at the beginning of an
inhalation cycle. The inhalator 30 includes a first inflow channel
34 and a second inflow channel 38. Each of the inflow channels are
disposed in communication with a blister pack 42, with one bister
44a and 44b being in disposed in communication with each inflow
channel.
[0081] The first inflow channel 34 and the second inflow channel 38
are disposed in communication with an inhalation channel 50 which
leads to a mouthpiece. While the first inflow channel 34 and the
second inflow channel 38 can be disposed to allow simultaneous
inhalation of the medicament in the blisters 44a and 44b, a flap 58
is disposed at the end of second inflow channel 38. The flap 58
initially inhibits airflow through the second inflow channel 38
caused by inhalation. Thus, inhalation initially draws medicament
from the blister 44b in the first inhalation channel 34. As the
inhalation draws the flap 58 open, the medicament in blister 44a is
able to flow through the second inflow channel 38. Depending on the
resistence of the flap 58 to opening, this can delay delivery of
the medicament in blister 44a until after inhalation of the
medicament in blister 44b is complete, or may only delay it
momentarily. Additionally, the flap 58 helps to ensure sufficient
inhalation rate is sufficient to increase the likelihood that the
medicament will be delivered to the appropriate portion of the
lung.
[0082] Turning now to FIG. 3A, there is shown a side
cross-sectional view of a single blister 60 made in accordance with
the principles of the present invention. The single blister 60
includes a first compartment 60a and a second compartment 60b which
keep two medicaments 64a and 64b separated until the blister is
lanced. Depending on the lancing mechanism, the medicament could be
delivered together or separately. The single blister 60 is
particularly advantageous because it can be used in existing
inhalers. The blister 60 could also be divided into three
compartments if desired to deliver three separate medications.
[0083] FIG. 3B shows a side cross-sectional view of dual blister 70
made in accordance with the principles of the present invention.
The dual blister includes a first blister 74a having a first
medicament 78a and a second blister 74b having a second medicament
78b. As shown in FIG. 3C, the two blisters can be lanced
simultaneously by a piercing mechanism 80, or can be pierced
separately. Airflow through the blisters 74a and 74b can then
transport the medicament 78a and 78b.
[0084] FIGS. 4A and 4B shows a blister pack disk 84 in which
blisters 88 containing a plurality of medications are all disposed
with a common radius on the blister pack disk. These blisters can
then be aligned with a pair of channels for delivering the
medicament as discussed above.
[0085] FIGS. 5A and 5B show a top view of an alternate embodiment
of a blister pack disk 90 and a side view of blister 94 thereof.
The disk has a plurality of blisters 94, each of which has two
compartments for holding the medicaments 98a and 98b. The
side-by-side compartments of the blisters 94 allow the medicament
to be accessed through a single airflow channel.
[0086] FIGS. 6A through 6C shows a top view of an alternate
configuration of a blister pack disk, and two side views of the
blisters thereof. The blister pack disk 100 has an outer ring of
blisters 104 and an inner ring of blisters 108. The outer blisters
104 are filled with a first medicament, and the inner blisters 108
are filled with a second medicament. As shown in FIG. 6A, the inner
blisters 108 and outer blisters can be disposed in radial alignment
so that they are in-line with a common airflow channel. By
controlling the location of the blisters 104, 108 and the
configuration of the blisters (see FIG. 6B and FIG. 6C) the
entrainment of the medicament in the inhaled air can be
controlled.
[0087] FIG. 7 shows a top view of an alternate configuration of a
blister pack disk 112. The blister pack disk 112 has a plurality of
blisters 114 for containing a first medicament and at least one
blister 118 for containing a second medicament. The configuration
allows for the delivery of two medicaments having different dosing
schedules from a single inhaler. For example, the medicament in
blisters 114 can be delivered daily, while the medicament in
blister 118 is delivered weekly. This can be achieved without the
patient being required to track the different dosing schedules,
because the second blister 118 only comes into alignment at the
appropriate time.
[0088] FIGS. 8A and 8B show top and side views of an alternate
configuration of a blister pack disk 120. The blister pack disks
have a plurality of groups of blisters 124, 126 and 128, with each
group being disposed at a different radius from the center of the
disk. This allows multiple medications to be delivered on a
periodic basis.
[0089] FIGS. 9A and 9B show top and side views of a blister card
132 having a first blister 134 with a first medicament and a second
blister 136 with a second medicament disposed side-by-side. The
blister card 134 can be inserted in an inhaler which uses separate
channels, such as shown in FIGS. 2A and 2B, or disposed in series
along a single channel.
[0090] FIG. 10A shows an exploded view of yet another blister pack
disk, generally indicated at 150, made in accordance with the
present invention. The blister pack disk 150 is formed by an outer
disk 154 of blisters containing a first medication, and an inner
disk 158 of blisters containing a second medication. Depending on
the configuration of the inhaler, the blisters of the outer disk
154 and the inner disk 158 can be in alignment, as shown in FIG.
10B, or can be offset from one another.
[0091] FIGS. 1A and 1B shows an exploded view of yet another
blister card 162. The blister card 162 is formed by a first
cross-shaped card 164 and a second cross-shaped card 166. The two
cards are then fused or otherwise attached to each other for
mounting in an inhaler as shown in FIG. 11A with the medicament in
an alternating pattern. By being formed of two parts in accordance
with the present invention, the blister 162 can be formed from
numerous different medicament combinations. It will also be
appreciated that two disks could be formed so that one disk has a
plurality of holes for receiving the blisters of the other disk.
Thus, the two disks could be formed separately to prevent
contamination between the two medicaments, and then joined to
provide a disk having alternating medications in the blisters.
[0092] Turning now to FIGS. 12A and 12B, there is shown yet another
embodiment of a blister pack disk 170 which is formed by a first
half 174 having a plurality of blisters 178 with a first
medicament, and a second half 180 having a plurality of blisters
184 having a second medicament. When combined, the halves can form
a single disk with opposed blisters having different medicaments.
The two halves 174 and 180 can be fused, crimped or attached in
numerous different manners which will be readily apparent to those
skilled in the art.
[0093] Thus there is disclosed an improved combined medicament
inhalation drug delivery system for treating and diagnosing
respiratory, systemic and topical diseases. Those skilled in the
art will appreciate numerous modifications that can be made without
departing from the scope and spirit of the present invention. The
appended claims are intended to cover such modifications.
* * * * *