U.S. patent application number 11/784969 was filed with the patent office on 2007-08-16 for osmotic pump with means for dissipating internal pressure.
Invention is credited to Craig R. Davis, Keith E. Dionne, Robert Mosbauer, John R. Peery.
Application Number | 20070191818 11/784969 |
Document ID | / |
Family ID | 33159637 |
Filed Date | 2007-08-16 |
United States Patent
Application |
20070191818 |
Kind Code |
A1 |
Dionne; Keith E. ; et
al. |
August 16, 2007 |
Osmotic pump with means for dissipating internal pressure
Abstract
The present invention includes an osmotic pump that includes a
means for venting an osmotic composition included in the pump
before the internal pressure of the pump has the opportunity to
build to such an extent that the pump is structurally compromised,
such as when one or more components of the pump are physically
separated. The means for venting osmotic material included in an
osmotic pump according to the present invention includes a vent
that allows the material included in the osmotic composition of the
pump to dissipate into an environment of operation at a rate that
results in dissipation of the pressure created within the osmotic
pump and a reduced potential for subject discomfort or
irritation.
Inventors: |
Dionne; Keith E.;
(Cambridge, MA) ; Mosbauer; Robert; (San
Francisco, CA) ; Davis; Craig R.; (Newark, CA)
; Peery; John R.; (Stanford, CA) |
Correspondence
Address: |
TRASK BRITT
P.O. BOX 2550
SALT LAKE CITY
UT
84110
US
|
Family ID: |
33159637 |
Appl. No.: |
11/784969 |
Filed: |
April 10, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
10814801 |
Mar 31, 2004 |
7207982 |
|
|
11784969 |
Apr 10, 2007 |
|
|
|
60459296 |
Mar 31, 2003 |
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Current U.S.
Class: |
604/890.1 |
Current CPC
Class: |
A61M 2005/14513
20130101; A61M 31/002 20130101; A61K 9/0004 20130101 |
Class at
Publication: |
604/890.1 |
International
Class: |
A61K 9/22 20060101
A61K009/22 |
Claims
1. An osmotic pump for providing sustained delivery of a beneficial
agent, comprising: a reservoir for holding the beneficial agent and
an osmotic agent; at least one wall defining a boundary of the
reservoir; at least one vent formed through the at least one wall;
and an impermeable material positioned to seal the at least one
vent, wherein the at least one vent is sealed from an environment
of operation by a water impermeable material that is readily
expelled as the at least one vent is exposed to the osmotic
agent.
2. The osmotic pump of claim 1, wherein the at least one vent is
sized to increase an exposed surface area of the semipermeable
membrane by less than 1%.
3. The osmotic pump of claim 1, wherein the at least one vent
comprises an annular orifice having a diameter of less than 0.01
inches.
4. The osmotic pump of claim 1, wherein the water impermeable
material comprises a wax or an oil.
5. The osmotic pump of claim 1, wherein the water impermeable
material is configured for progressive expulsion when a threshold
pressure in the osmotic pump is reached.
6. The osmotic pump of claim 1, wherein the reservoir is made of a
non-bioerodible material.
7. The osmotic pump of claim 1, wherein the osmotic agent comprises
an osmotic tablet.
8. The osmotic pump of claim 1, wherein the osmotic agent comprises
an osmagent, an osmopolymer, or mixtures thereof.
9. The osmotic pump of claim 1, further comprising a filler
distributed within the reservoir and around the osmotic agent.
10. The osmotic pump of claim 1, further comprising a movable
piston located in the reservoir and between the beneficial agent
and the osmotic agent.
11. The osmotic pump of claim 10, wherein the movable piston is
formed of a noncompressible material.
12. The osmotic pump of claim 1, wherein the beneficial agent is
selected from the group consisting of medicaments, vitamins,
nutrients, biocides, sterilization agents, food supplements, sex
sterilants, fertility inhibitors, fertility promoters, and
combinations thereof.
13. The osmotic pump of claim 1, wherein the beneficial agent is
formulated as a slurry, a suspension, or a solution.
14. An implantable osmotic pump for providing sustained delivery of
a beneficial agent, comprising: a reservoir for holding the
beneficial agent and an osmotic agent; and a means for venting the
osmotic agent out of the reservoir upon displacement of a water
impermeable material when a threshold pressure in the osmotic pump
is reached.
15. The implantable osmotic pump of claim 14, wherein the means for
venting the osmotic agent comprises a vent formed through a
reservoir wall.
16. The implantable osmotic pump of claim 14, wherein the means for
venting the osmotic agent comprises a plurality of vents formed
through one or more walls that define boundaries of the
reservoir.
17. An osmotic pump for providing sustained delivery of a
beneficial agent, comprising: a reservoir for holding the
beneficial agent and an osmotic agent; at least one wall defining a
boundary of the reservoir; at least one vent formed through the at
least one wall; and a means for removably sealing the at least one
vent, the sealing means being capable of expulsion from the at
least one vent when a threshold pressure in the osmotic pump is
reached and capable of releasing at least a portion of the osmotic
agent from the reservoir.
18. The osmotic pump of claim 20, wherein the sealing means
comprises a water impermeable material.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of application Ser. No.
10/814,801, filed Mar. 31, 2004, pending, which claims the benefit
of the filing date of provisional patent application Ser. No.
60/459,296, filed Mar. 31, 2003, for "Osmotic Pump With Means For
Dissipating Internal Pressure." The disclosure of each of the
previously referenced U.S. patent applications is hereby
incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to implantable osmotic pumps
providing sustained delivery of a drug. In particular, the present
invention is directed to an implantable osmotic pump including a
vent that allows gradual venting of osmotic material after the drug
formulation included in the osmotic pump is delivered.
BACKGROUND
[0003] Implantable, controlled-release osmotic pumps (hereinafter
"osmotic pumps") are known in the art. For example, U.S. Pat. Nos.
3,797,492, 3,987,790, 4,008,719, 4,865,845, 5,057,318, 5,059,423,
5,112,614, 5,137,727, 5,151,093, 5,234,692, 5,234,693, 5,279,608,
5,336,057, 5,728,396, 5,985,305, 5,997,527, 5,997,902, 6,113,938,
6,132,420, 6,217,906, 6,261,584, 6,270,787, and 6,375,978, which
are assigned to ALZA Corporation of Mountain View, Calif., and are
herein incorporated in their entirety by reference, describe
various osmotic pumps. The osmotic pumps described in these
references may be designed for implantation in a subject of choice
and may be configured to deliver a range of drugs at various rates
over predetermined periods of time.
[0004] Osmotic pumps typically include a reservoir for containing
an amount of drug formulation, an osmotic composition, a
semipermeable membrane, a delivery orifice, and a piston separating
the drug formulation from the osmotic composition. Upon
administration to an environment of operation, water is drawn
through the semipermeable membrane of the osmotic pump into the
osmotic composition, causing the osmotic composition to swell. As
the osmotic composition swells, the piston included in the osmotic
pump is driven through its stroke, resulting in the expulsion of
the drug formulation at a controlled rate through the delivery
orifice. The rate of drug release from an osmotic pump may be
adjusted by altering the composition or amount of the drug
formulation or the osmotic composition included in the osmotic
pump. Alternatively, the release rate of drug formulation provided
by an osmotic pump may be adjusted by altering the composition or
exposed surface area of the semipermeable membrane. Because they
allow the controlled delivery of active agent over periods of
weeks, months, or even years, osmotic pumps can advantageously
provide long-term dosing of a desired drug without requiring
frequent visits to a healthcare provider or repetitive
self-medication. Therefore, osmotic pumps can work to provide
increased patient compliance, reduced irritation at the site of
administration, fewer occupational hazards for healthcare
providers, reduced waste hazards, and increased therapeutic
efficacy through enhanced dosing control.
[0005] As drug formulation is delivered from an osmotic pump, the
internal pressure generated by the osmotic composition within the
pump generally remains relatively low. However, if an osmotic
system is left within an environment of operation after the piston
included in the osmotic pump reaches the end of its stroke within
the reservoir (e.g., after substantially all the drug formulation
has been delivered), the osmotic composition will continue to draw
water in from the environment of operation. As water is drawn into
the osmotic pump without expulsion of a corresponding amount of
drug formulation, the pressure within the system may rise to such
an extent that a component of the osmotic pump is compromised or
physically separated. Where the semipermeable membrane included in
an osmotic pump is held in place through a friction fit, such as is
described in, for example, U.S. Pat. Nos. 5,985,305, 5,728,396, and
6,156,331, the semipermeable membrane is one of the components that
is most likely to be separated from the osmotic pump if the
internal pressure of the osmotic system increases well beyond
normal operational pressures.
[0006] It would, therefore, be an improvement in the art to provide
an osmotic pump that allows the placement of a semipermeable
membrane through a friction fit mechanism, yet works to prevent a
pressure build-up within the pump that results in the dissociation
of pump components, such as the semipermeable membrane. Though not
likely to be harmful to a subject, the physical separation of one
or more components of an implanted osmotic pump may complicate
removal of the device from a subject. Moreover, the physical
separation of the semipermeable membrane of an osmotic pump may
allow a relatively sudden release of the material forming the
osmotic composition, which may result in localized discomfort or
inflammation. Thus, where an implantable osmotic pump is designed
to dissipate internal pressure before such pressure reaches a level
that could cause dissociation of one or more parts, the design of
the osmotic pump would ideally allow pressure dissipation without
causing a release of osmotic material that results in discomfort or
inflammation.
SUMMARY OF THE INVENTION
[0007] The present invention is directed to an osmotic pump that
includes a means for venting the osmotic composition included
therein before the internal pressure of the pump has the
opportunity to build to such an extent that the pump is
structurally compromised, such as when one or more components of
the pump are physically separated. The means for venting osmotic
material included in an osmotic pump according to the present
invention includes a vent that allows the material included in the
osmotic composition of the pump to dissipate into an environment of
operation, resulting in a reduction of the internal pressure
[0008] The vent included in an osmotic pump of the present
invention is formed through the reservoir of the osmotic pump and
is positioned such that the vent is sealed from the osmotic
composition under normal operating conditions. However, the vent is
also positioned in the reservoir such that, if the pressure within
the osmotic pump reaches a magnitude that results in displacement
of one or more components, the vent is opened or exposed to the
materials forming the osmotic composition, which allows release of
materials forming the osmotic composition into the environment of
operation and results in the dissipation of the internal pressure
before one or more components of the osmotic pump fails or is
separated from the device. In addition, because an osmotic pump
according to the present invention can be designed without
compressive elements, the maximum rate of material expulsion from
the vent will typically match the targeted release rate of the
osmotic pump. Therefore, an osmotic pump according to the present
invention can be easily designed to allow venting of the osmotic
composition, while reducing or minimizing the likelihood that such
venting will result in discomfort or irritation to the subject.
[0009] In a preferred embodiment, an osmotic pump includes a vent
that is sealed by the semipermeable membrane of the osmotic pump
during normal operating conditions. The semipermeable membrane of
such an embodiment is friction fit within the reservoir and is
designed to allow progressive displacement of the semipermeable
membrane once a threshold pressure is reached within the osmotic
pump. The vent included in this embodiment of the present invention
is positioned such that, if the internal pressure reaches the
threshold pressure and the semipermeable membrane begins to be
displaced relative to the reservoir, the vent is exposed well
before the semipermeable membrane is separated from the device.
Once the vent is exposed, the osmotic materials included in the
osmotic composition may be expelled from the osmotic pump,
resulting in a decrease in pressure within the pump and preventing
separation of the semipermeable membrane.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The present invention is described with reference to the
accompanying drawings in which like elements bear like reference
numerals, and wherein:
[0011] FIG. 1 provides a schematic illustration of one embodiment
of an osmotic pump according to the present invention.
[0012] FIG. 2 provides a schematic illustration of the osmotic pump
shown in FIG. 1 as the pump functions to deliver drug formulation
to an environment of operation.
[0013] FIG. 3 provides a schematic illustration of the osmotic pump
shown in FIG. 1 and FIG. 2 as delivery of the drug formulation is
completed and the piston included in the osmotic pump reaches the
end of its stroke within the reservoir.
[0014] FIG. 4 provides a schematic illustration of the osmotic pump
shown in FIG. 1 through FIG. 3 after the internal pressure of the
osmotic pump has caused displacement of the semipermeable membrane,
the vent has been exposed, and the osmotic composition is venting
into the environment of operation.
DETAILED DESCRIPTION OF THE INVENTION
[0015] An osmotic pump 10 according to the present invention is
illustrated in FIG. 1. As can be seen by reference to these
figures, an osmotic pump 10 according to the present invention
includes a reservoir 12, a drug formulation 14, an osmotic
composition 16, a piston 18, a semipermeable membrane 22, a
delivery orifice 24, and a vent 26 formed through the wall 20 of
the reservoir 12. However, the configuration of the osmotic pump 10
illustrated in FIG. 1 provides only one example of an osmotic pump
according to the present invention and is not to be construed as
limiting the present invention. The present invention is generally
applicable to osmotic pumps, and an osmotic pump according to the
present invention may be designed to conform to a wide range of
desired sizes or shapes. Moreover, an osmotic pump according to the
present invention may be designed for application in various
environments or administration by various routes, such as by oral
administration, ruminal administration, or implantation.
[0016] The reservoir 12 of the osmotic pump 10 of the present
invention may be sized and shaped as desired to suit a desired
application or to facilitate placement of the osmotic pump 10 in a
desired environment of operation. Materials suitable for forming
the reservoir 12 must be sufficiently strong to ensure that the
reservoir 12 does not leak, crack, break, or significantly distort
under stresses to which it is subjected to during administration
and operation of the osmotic pump 10. In particular, the reservoir
12 is formed of a material that is sufficiently rigid to withstand
expansion of the osmotic composition 16 without undergoing
substantial changes to the size or shape of the reservoir 12. The
material used to form the reservoir 12 is also chosen to be largely
impermeable to fluids from the environment of operation and to the
material constituents included in the drug formulation 14 and the
osmotic composition 16. As it is used herein the term "largely
impermeable" indicates that the migration of materials into or out
of the osmotic pump through the material forming the reservoir 12
is so low that any such migration of materials has substantially no
adverse impact on the function of the device.
[0017] The material used to form the reservoir 12 of an osmotic
pump 10 according to the present invention is preferably not a
bioerodible material and will remain intact even after the drug
formulation 14 has been delivered. Such a design facilitates
recovery or passage of the osmotic pump 10 after the drug
formulation 14 contained therein has been delivered to a subject.
Typical materials suitable for the construction of the reservoir 12
of an osmotic pump 10 according to the present invention include,
but are not limited to, nonreactive polymers and biocompatible
metals and alloys. Specific examples of suitable polymers include,
but are not limited to, polyimide, polysulfone, polycarbonate,
polyethylene, polypropylene, polyvinylchloride-acrylic copolymer,
polycarbonate-acrylonitrile-butadiene-styrene, polystyrene,
acrylonitrile polymers, such as acrylonitrile-butadiene-styrene
terpolymer and the like, halogenated polymers, such as
polytetrafluoroethylene, polychlorotrifluoroethylene copolymer,
tetrafluoroethylene and hexafluoropropylene. Metallic materials
useful in forming the reservoir 12 include, but are not limited to,
stainless steel, titanium, platinum, tantalum, gold, and their
alloys, as well as gold-plated ferrous alloys, platinum-plated
ferrous alloys, cobalt-chromium alloys, and titanium nitride coated
stainless steel.
[0018] The semipermeable membrane 22 included in an osmotic pump 10
of the present invention is formulated and prepared to be permeable
to the passage of external liquids, such as water and biological
liquids, but substantially impermeable to the passage of the drug,
osmopolymers, osmagents, and the like that may be included in the
osmotic pump 10. Suitable materials and methods for forming the
semipermeable membrane 22 included in an osmotic pump 10 of the
present invention are well known in the art and are detailed in,
for example, U.S. Pat. Nos. 3,797,492, 3,987,790, 4,008,719,
4,865,845, 4,874,388, 5,057,318, 5,059,423, 5,112,614, 5,137,727,
5,151,093, 5,234,692, 5,234,693, 5,279,608, 5,336,057, 5,728,396,
5,985,305, 5,997,527, 5,997,902, 6,113,938, 6,132,420, 6,217,906,
6,261,584, 6,270,787, and 6,375,978, the contents of which are
herein incorporated in their entirety by this reference. Such
possible semipermeable materials from which the semipermeable
membrane 22 can be made include, but are not limited to, for
example, Hytrel polyester elastomers (DuPont), cellulose esters,
cellulose ethers, and cellulose ester-ethers, water flux enhanced
ethylene-vinyl acetate copolymers, semipermeable membranes made by
blending a rigid polymer with water-soluble low molecular weight
compounds, and other semipermeable materials well known in the art.
The above cellulosic polymers have a degree of substitution, D.S.,
on the anhydroglucose unit, from greater than 0 up to 3 inclusive.
By "degree of substitution," or "D.S.," is meant the average number
of hydroxyl groups originally present on the anhydroglucose unit
comprising the cellulose polymer that is replaced by a substituting
group. Representative materials include, but are not limited to,
one selected from the group consisting of cellulose acylate,
cellulose diacylate, cellulose triacylate, cellulose acetate,
cellulose diacetate, cellulose triacetate, mono-, di-, and
tricellulose alkanylates, mono-, di-, and tricellulose aroylates,
and the like. Exemplary cellulosic polymers include cellulose
acetate having a D.S. up to 1 and an acetyl content up to 21%;
cellulose acetate having a D.S. of 1 to 2 and an acetyl content of
21% to 35%; cellulose acetate having a D.S. of 2 to 3 and an acetyl
content of 35% to 44.8%, and the like. More specific cellulosic
polymers include cellulose propionate having a D.S. of 1.8 and a
propionyl content of 39.2% to 45% and a hydroxyl content of 2.8% to
5.4%; cellulose acetate butyrate having a D.S. of 1.8 and an acetyl
content of 13% to 15% and a butyryl content of 34% to 39%;
cellulose acetate butyrate having an acetyl content of 2% to 29%, a
butyryl content of 17% to 53%, and a hydroxyl content of 0.5% to
4.7%; cellulose acetate butyrate having a D.S. of 1.8, an acetyl
content of 4% average weight percent, and a butyryl content of 51%;
cellulose triacylates having a D.S. of 2.9 to 3 such as cellulose
trivalerate, cellulose trilaurate, cellulose tripalmitate,
cellulose trisuccinate, and cellulose trioctanoate; cellulose
diacylates having a D.S. of 2.2 to 2.6 such as cellulose
disuccinate, cellulose dipalmitate, cellulose dioctanoate,
cellulose dipentate; coesters of cellulose, such as cellulose
acetate butyrate and cellulose, cellulose acetate propionate, and
the like. Other materials that may be used to prepare a
semipermeable membrane 22 useful in the osmotic pump 10 of the
present invention include polyurethane, polyetherblockamide (PEBAX,
commercially available from ELF ATOCHEM, Inc.), and
injection-moldable thermoplastic polymers with some hydrophilicity
such as ethylene vinyl alcohol (EVA).
[0019] The osmotic composition 16 included in the osmotic pump 10
of the present invention may be formed of any material that creates
sufficient osmotic pressure to draw water into the osmotic
composition 16 through the semipermeable membrane 22 such that the
osmotic composition 16 causes delivery of the drug formulation 14
at a desired rate over a preselected period of time. Preferably,
the osmotic composition 16 is formed as one or more osmotic tablets
formed of an initially solid or nonflowable composition. However,
the osmotic composition 16 included in an osmotic pump 10 according
to the present invention is not limited to a tableted and initially
solid or nonflowable composition. The osmotic composition 16 loaded
into a reservoir 12 of an osmotic pump 10 according to the present
invention may be formed in any suitable shape, texture, density,
and consistency. For example, instead of a solid, tableted
composition, it is possible that the osmotic composition 16 may be
loaded into the reservoir 12 as a powdered material.
[0020] The osmotic composition 16 includes an osmotic agent. The
osmotic agent included in the osmotic composition is a
water-attracting agent that serves to draw water into the osmotic
pump 10 through the semipermeable membrane 22 and drive the flow of
drug formulation 14 out from the osmotic pump 10. The osmotic agent
included in the osmotic composition 16 may be an osmagent, an
osmopolymer, or a mixture of the two. Methods and formulations for
providing osmotic compositions that are suitable for use in an
osmotic pump according to the present invention are well known. For
example, the patent references that are cited and incorporated by
reference herein detail methods and materials suitable for forming
osmotic compositions that may be used in an osmotic pump 10
according to the present invention.
[0021] Materials that fall within the category of osmagent include
materials that are nonvolatile, soluble in water, and create an
osmotic gradient suitable for driving the influx of water into the
osmotic pump 10. Examples of osmagents that may be useful in the
osmotic composition 16 of an osmotic pump 10 of the present
invention include, but are not limited to, magnesium sulfate,
magnesium chloride, sodium sulfate, lithium sulfate, sodium
phosphate, potassium phosphate, d-mannitol, sorbitol, inositol,
urea, magnesium succinate, tartaric acid, raffinose, and various
monosaccharides, oligosaccharides, and polysaccharides, such as
sucrose, glucose, lactose, fructose, and dextran, as well as
mixtures of any of these various species.
[0022] Materials that fall within the category of osmopolymer are
hydrophilic polymers that swell upon contact with water.
Osmopolymers may be natural (i.e., of plant or animal origin) or
synthetic, and examples of osmopolymers are well known in the art.
Particular osmopolymers that may be used in the osmotic composition
16 of an osmotic pump 10 of the present invention include, but are
not limited to, poly(hydroxy-alkyl methacrylates) with molecular
weights of 30,000 to 5,000,000, poly(vinylpyrrolidone) with
molecular weights of 10,000 to 360,000, anionic and cationic
hydrogels, polyelectrolyte complexes, poly(vinyl alcohol) having
low acetate residual, optionally cross linked with glyoxal,
formaldehyde or glutaraldehyde and having a degree of
polymerization of 200 to 30,000, a mixture of methyl cellulose,
cross linked agar and carboxymethylcellulose, a mixture of
hydroxypropyl methylcellulose and sodium carboxymethylcellulose,
polymers of N-vinyllactams, polyoxyethylene-polyoxypropylene gels,
polyoxybutylene-polyethylene block copolymer gels, carob gum,
polyacrylic gels, polyester gels, polyurea gels, polyether gels,
polyamide gels, polypeptide gels, polyamino acid gels,
polycellulosic gels, Carbopol.RTM. acidic carboxy polymers having
molecular weights of 80,000 to 200,000, Polyox Polyethylene oxide
polymers having molecular weights of 10,000 to 5,000,000, starch
graft copolymers, and Aqua-Keeps.TM. acrylate polymer
polysaccharides.
[0023] In addition to an osmotic composition 16, an osmotic pump 10
according to the present invention may also include an additive or
filler 28 distributed around the osmotic composition 16. This
filler 28 may be any flowable composition, such as a liquid or gel
composition, which is substantially incompressible, is suitable for
use in the intended environment of operation, is compatible with
the other components of the osmotic pump, works to displace air or
gas from around the osmotic composition 16, and does not cause the
osmotic composition 16 to swell and freeze-up, as described in U.S.
Pat. No. 6,132,420. Materials and methods suitable for providing a
filler 28 suitable for use in an osmotic pump according to the
present invention are also described in U.S. Pat. No. 6,132,420,
the contents of which are herein incorporated in their entirety by
reference.
[0024] The use of a filler 28 is particularly helpful where the
osmotic composition 16 is formed as a tableted composition.
Machining and tableting tolerances require that there be a gap
between the osmotic composition 16 and the surrounding reservoir
wall 20. Small irregularities in the shape or contour of the
tableted material may also create a gap between the osmotic
composition 16 and a piston 18 included in an osmotic pump 10
according to the invention. Such gaps, which can typically range
from between about 0.001 to 0.1 inches, are filled with air or
other gaseous material, and even the smallest of such air gaps can
create a start-up delay of several days to weeks. Additionally,
air-filled gaps problematically affect the delivery rate of drug
formulation when the osmotic pump is subjected to different
external pressures, such as when a patient with an implanted
osmotic pump scuba dives or travels to higher altitudes. The
inclusion of a filler 28 serves to reduce or eliminate the extent
to which any gaps around the osmotic composition 16 are filled with
air or another gaseous material and, thereby, works to reduce or
eliminate the delays and drug delivery inconsistencies that such
gaps can produce.
[0025] The movable piston 18 included in an osmotic pump 10
according to the present invention is configured to fit within the
reservoir 12 in a sealed manner that allows the piston 18 to be
displaced within the reservoir 12 as water is taken into the
osmotic composition 16 and the osmotic composition 16 expands. In a
preferred embodiment, the piston 18 is formed of a substantially
noncompressible material. Moreover, a piston 18 suitable for use in
an osmotic pump 10 of the present invention is preferably formed of
a material that is impermeable to the osmotic composition 16 and
the drug formulation 14, and may include one or more protrusions,
which work to form a seal between the piston 18 and the wall 20 of
the reservoir 12. Materials suitable for use in a piston 18
included in an osmotic pump 10 of the present invention include
metallic materials, such as metal alloys, elastomeric materials,
such as the nonreactive polymers already mentioned herein, as well
as elastomers in general, such as polyurethanes, polyamides,
chlorinated rubbers, styrene-butadiene rubbers, and chloroprene
rubbers.
[0026] As can be seen by reference to FIG. 1, the delivery orifice
24 included in an osmotic pump 10 of the present invention may
simply include an orifice formed through one end of the wall 20 of
the reservoir 12. Such a delivery orifice 24 can be provided using,
for example, known molding methods or known mechanical or laser
drilling methods. If desired, the reservoir 12 of an osmotic pump
10 of the present invention may include more than one delivery
orifice 24. In an alternative embodiment, the delivery orifice 24
of an osmotic pump 10 of the present invention may be formed by an
outlet plug (not illustrated) that is positioned at least partially
within the reservoir 12. Such an outlet plug may be configured, for
example, to provide a delivery orifice 24 that optimizes flow of
drug formulation 14 or to regulate back diffusion of environmental
fluids into the osmotic pump 10. Where the delivery orifice 24 of
the osmotic pump 10 of the present invention is formed by an outlet
plug, however, the outlet plug is prepared from a substantially
noncompressible material. Outlet plugs suitable for application in
an osmotic pump according to the present invention are known in the
art and are described in, for example, U.S. Pat. Nos. 5,985,305,
6,217,906, and 5,997,527, the contents of each of which are herein
incorporated in their entirety by reference. The dimensions of the
delivery orifice 24, in terms of both diameter and length, will
vary depending on, among other factors, the type of drug delivered,
the rate at which the drug formulation 14 is expelled from the
osmotic pump 10, and the environment into which it is to be
delivered.
[0027] Although osmotic pumps according to the present invention
are preferably designed for and administered to human or animal
physiological environments, osmotic pumps according to the present
invention are generally applicable for the delivery of beneficial
agents to an environment of operation and are not limited in
utility to physiological environments. For example, the osmotic
pumps according to the present invention may be used in intravenous
systems (e.g., attached to an IV pump, and IV bag, or an IV bottle)
for delivering beneficial agents to animals or humans, systems for
blood oxygenation, kidney dialysis or electrophoresis, systems for
delivering, for instance, nutrients or growth regulating compounds
to cell cultures, as well as in pools, tanks, reservoirs and the
like. Therefore, the osmotic pump 10 of the present invention is
applicable to the delivery of beneficial agents in general, and the
term "drug" as it is used herein refers to any beneficial agent
that may be delivered to an environment of operation and includes,
but is not limited to, medicaments, vitamins, nutrients, biocides,
sterilization agents, food supplements, sex sterilants, fertility
inhibitors, and fertility promoters. Specific drugs that may be
delivered by osmotic pumps of the present invention are detailed,
for example, in U.S. Pat. Nos. 6,132,420, the contents of which are
incorporated herein by this reference. Additional examples of drugs
that may be delivered by an osmotic pump 10 according to the
present invention can be found in the other patent references that
are cited and incorporated by reference herein.
[0028] The drug included in the drug formulation 14 contained
within an osmotic pump 10 of the present invention can be present
in a wide variety of chemical and physical forms. At the molecular
level, the drug may be present as an uncharged molecule, molecular
complex, or pharmaceutically acceptable acid addition or base
addition salts, such as hydrochlorides, hydrobromides, sulfate,
laurylate, oleate, and salicylate. Salts of metals, amines or
organic cations may be used for acidic drug compounds. Derivatives
of drugs, such as esters, ethers, and amides can also be used.
Moreover, the drug formulation 14 included in an osmotic pump 10
according to the present invention may include more than one drug,
resulting in an osmotic pump 10 capable of delivering multiple
drugs during its functional lifetime.
[0029] The drug formulation 14 included in an osmotic pump 10
according to the present invention may include any formulation
suitable for delivering a drug from an osmotic pump 10 according to
the present invention. The drug formulation 14 may be formulated as
any flowable composition, such as a slurry, a suspension, or a
solution, capable of delivering the desired drug to a chosen
environment of operation. As desired, the drug formulation 14
included in an osmotic pump 10 according to the present invention
may include one or more of various ingredients that work to allow
delivery of the drug to the desired environment of operation. In
particular, the drug formulation 14 included in an osmotic pump
according to the present invention may optionally include
preservatives, such as one or more antioxidants or other
stabilizing agent, permeation enhancers, or carrier materials that
are application appropriate. For example, if the osmotic pump is
designed for implantation to a human or animal subject, any
carrier, preservative, or permeation enhancer used would be a
pharmaceutically acceptable material.
[0030] As can be seen by reference to FIG. 1, the vent 26 included
in an osmotic pump 10 according to the present invention is formed
through the wall 20 of the reservoir 12. The vent 26 may be formed
by any suitable method, such as by mechanical drilling, laser
drilling, molding, or any other known method that may be used to
provide a vent 26 of a desired size and shape through the material
forming the reservoir 12. The vent 26 is positioned in the
reservoir 12 of an osmotic pump according to the present invention
such that, during normal operation, it is sealed from the osmotic
composition 16 under normal operating conditions. However, the vent
26 is also positioned in the reservoir 12 such that, if the
pressure within the osmotic pump 10 reaches a magnitude that causes
displacement of one or more components, the vent 26 is opened or
exposed, allowing the internal pressure of the osmotic pump 10 to
dissipate before one or more components are separated from the
osmotic pump 10.
[0031] An osmotic pump 10 according to the present invention
preferably includes a vent 26 that is initially sealed by the
semipermeable membrane 22. In such an embodiment, the semipermeable
membrane 22 is friction fit within the reservoir 12 and both the
reservoir 12 and the semipermeable membrane 22 are configured such
that, as a threshold pressure is reached within the osmotic pump
10, the semipermeable membrane 22 is progressively displaced from
within the reservoir 12. As it is used herein, the term "threshold
pressure" indicates an internal pressure or range of pressures that
will cause the semipermeable membrane 22 included in the osmotic
pump 10 to begin to be displaced within the reservoir 12, but will
not result in immediate separation of the semipermeable membrane 22
from the osmotic pump 10. The materials and configuration of both
the semipermeable membrane 22 and the reservoir 12 may be altered,
as desired, to achieve a semipermeable membrane that is
progressively displaced at different threshold pressures. For
instance, the semipermeable membrane 22 may be configured as a plug
with multiple retaining rings (not shown) that function to increase
the threshold pressure of the semipermeable membrane and work to
facilitate progressive expulsion once the threshold pressure is
reached.
[0032] The position of the vent 26 in the reservoir 12 is chosen to
provide a vent 26 that is effectively sealed by the semipermeable
membrane 22 during normal operation of the osmotic pump 10.
However, the vent 26 is also positioned to ensure the vent 26 is
opened if the internal pressure of the osmotic pump 10 reaches or
exceeds the threshold pressure for the semipermeable membrane 22.
As the vent is opened, the osmotic material included in the osmotic
composition 16 is released into the environment of operation,
resulting in the dissipation of the internal pressure below the
threshold pressure required to displace the semipermeable membrane
22. The positioning of the vent 26 is chosen to ensure venting of
the osmotic composition 16 and dissipation of the internal pressure
before the semipermeable membrane 22 is displaced to such a degree
that the semipermeable membrane 22 could separate from the osmotic
pump when subjected to mechanical, chemical, or thermal stresses
that are typical of the chosen environment of operation.
[0033] Because the rate at which water is imbibed into an osmotic
pump 10 according to the present invention depends, at least in
part, on the surface area of the semipermeable membrane 22 that is
exposed to the environment of operation, the vent 26 included in an
osmotic pump 10 of the present invention has the potential to
affect release rate performance. Where the osmotic pump 10
according to the present invention is configured such that the vent
26 allows aqueous liquid from the environment of operation to
contact the semipermeable membrane 22 during normal operation, the
increase in exposed surface area provided by the vent 26 will
result in an increase in the rate at which water permeates and
flows through the semipermeable membrane 22. As a result, an
osmotic pump 10 according to the present invention may exhibit
relatively shorter start-up times and relatively faster release
rates when compared to an osmotic pump that does not include a vent
26 or an osmotic pump that includes a vent that is protected from
the environment of operation. Nevertheless, the liquid permeation
rate and release rate performance of an osmotic pump 10 according
to the present invention can be preselected and controlled through,
for example, selection or alteration of the materials used to form
the semipermeable membrane, the geometry of the semipermeable
membrane, and the surface area and location of the exposed portions
of the semipermeable membrane.
[0034] In addition, the potential impact that a vent 26 may have on
the permeation or release rate provided by the semipermeable
membrane 22 of the osmotic pump 10 of the present invention can be
mitigated or avoided altogether. For example, as the size of the
vent 26 included in an osmotic pump 10 according to the present
invention decreases, any affect that the vent 26 has on the
permeation rate of the semipermeable membrane 22 or the release
rate of the osmotic pump 10 also decreases. Therefore, in a
preferred embodiment, the vent 26 included in an osmotic pump 10
according to the present invention is sized such that the vent 26
increases the exposed surface area of the semipermeable membrane 22
by less than 1% relative to an identical device that does not
include the vent 26. In an alternative embodiment, the vent 26
included in the osmotic pump 10 of the present invention is formed
as a generally annular orifice that has a diameter of less than
0.01 inches. To avoid altogether any changes in permeation or
release rates that may be caused by the vent 26 included in an
osmotic pump 10 of the present invention, the vent 26 may be sealed
from the environment of operation by a water impermeable material,
such as a wax or an oil, that is readily expelled as the vent 26 is
opened and osmotic material is released.
[0035] FIG. 2 through FIG. 4 illustrate the general function of an
osmotic pump 10 according to the present invention. Once an osmotic
pump 10 of the present invention is placed in an environment of
operation, aqueous fluid is imbibed through the semipermeable
membrane 22 at a predetermined rate into the osmotic composition
16. As can be seen in FIG. 2, as osmotic composition 16 takes up
water, the osmotic composition 16 expands and acts against the
piston 18, driving the piston 18 through its stroke within the
reservoir 12. As the piston 18 is driven through its stroke, the
drug formulation 14 is expelled from the osmotic pump 10 at a
controlled rate through the delivery orifice 24. Typically, the
drug formulation 14 is released from the osmotic pump 10 at a rate
equal to the rate at which water is imbibed into the system, and,
as a result, the pressure within the osmotic pump 10 remains
relatively low as the osmotic pump 10 operates to deliver drug
formulation 14 at a controlled rate over time.
[0036] After the piston 18 reaches the end of its stroke within the
reservoir 12 and the drug formulation has been delivered from the
osmotic pump 10 (shown in FIG. 3), water will continue to be taken
up through the semipermeable membrane 22. As water continues to be
taken into the osmotic composition 16, the internal pressure of the
osmotic pump 10 will continue to build, until the threshold
pressure for the semipermeable membrane 22 is reached. As is shown
in FIG. 4, once the threshold pressure is reached, the
semipermeable membrane 22 is displaced and the vent 26 is opened or
exposed such that the osmotic material included in the osmotic
composition 16 is released through the vent 26 and into the
environment of operation. As osmotic materials are released through
the vent 26, the internal pressure of the osmotic pump 10 decreases
below the threshold pressure, and the displacement of the
semipermeable membrane ceases.
[0037] The design of the osmotic pump 10 of the present invention
not only works to allow venting of the osmotic composition and
dissipation of internal pressure, but the design of osmotic pump 10
of the present invention allows such performance to be achieved
without causing a release of osmotic material that would result in
discomfort or irritation to the subject. In particular, the
components of the osmotic pump 10 are designed to be substantially
incompressible. As a result, when the pressure within the osmotic
pump 10 builds to the extent that the vent 26 is opened, there is
no decompression that may otherwise result in the immediate release
of an amount of osmotic material that could result in localized
irritation or discomfort. Instead, where the vent 26 included in
the osmotic pump 10 is opened, the osmotic composition 14 will
typically be delivered from the osmotic pump 10 at a maximum rate
that is equal to the maximum release rate provided by the osmotic
pump 10. Moreover, as the osmotic composition 14 is released
through the vent 26, the osmotic composition 14 becomes more dilute
and a smaller osmotic gradient is produced across the semipermeable
membrane 22, resulting in an exponential decrease in the mass of
osmotic material released over time. Therefore, in each of its
embodiments, the osmotic pump 10 of the present invention not only
works to dissipate internal pressure before it becomes undesirably
high, but the design of the osmotic pump 10 allows such dissipation
to occur in a way that reduces the risk of discomfort to the
subject.
* * * * *