GB2048710A - Osmotically Driven Fluid Dispenser - Google Patents
Osmotically Driven Fluid Dispenser Download PDFInfo
- Publication number
- GB2048710A GB2048710A GB8011264A GB8011264A GB2048710A GB 2048710 A GB2048710 A GB 2048710A GB 8011264 A GB8011264 A GB 8011264A GB 8011264 A GB8011264 A GB 8011264A GB 2048710 A GB2048710 A GB 2048710A
- Authority
- GB
- United Kingdom
- Prior art keywords
- bag
- dispenser
- weight
- osmotically effective
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000012530 fluid Substances 0.000 title claims description 30
- 239000012528 membrane Substances 0.000 claims abstract description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000006185 dispersion Substances 0.000 claims abstract description 6
- 229920001169 thermoplastic Polymers 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 41
- -1 poly(ethylene oxide) Polymers 0.000 claims description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 229920000642 polymer Polymers 0.000 claims description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 235000012239 silicon dioxide Nutrition 0.000 claims description 2
- 239000000377 silicon dioxide Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 10
- 229940079593 drug Drugs 0.000 abstract description 10
- 238000011049 filling Methods 0.000 abstract description 9
- 230000003204 osmotic effect Effects 0.000 description 14
- 239000000243 solution Substances 0.000 description 9
- 239000013543 active substance Substances 0.000 description 8
- 238000000034 method Methods 0.000 description 6
- 238000000576 coating method Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000011248 coating agent Substances 0.000 description 4
- 238000001746 injection moulding Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 238000007598 dipping method Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229920003048 styrene butadiene rubber Polymers 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 238000004026 adhesive bonding Methods 0.000 description 2
- 229920006217 cellulose acetate butyrate Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000035558 fertility Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000005086 pumping Methods 0.000 description 2
- 238000003856 thermoforming Methods 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 229920002633 Kraton (polymer) Polymers 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000003619 algicide Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000003139 biocide Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 238000000748 compression moulding Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 230000002070 germicidal effect Effects 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000007952 growth promoter Substances 0.000 description 1
- 230000002706 hydrostatic effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 239000002917 insecticide Substances 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000012633 leachable Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 239000002373 plant growth inhibitor Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920002285 poly(styrene-co-acrylonitrile) Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000003128 rodenticide Substances 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
- B01D61/002—Forward osmosis or direct osmosis
- B01D61/0022—Apparatus therefor
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
- A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
Landscapes
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Water Supply & Treatment (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Anesthesiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Infusion, Injection, And Reservoir Apparatuses (AREA)
- Medicinal Preparation (AREA)
- Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
- Catching Or Destruction (AREA)
- Formation And Processing Of Food Products (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Cosmetics (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Containers And Packaging Bodies Having A Special Means To Remove Contents (AREA)
Abstract
An osmotically driven minipump that is used to administer inter alia drug solutions, comprises an inner flexible bag (14) that holds the drug solution (18); a plug (15) having a recessed inner end (26) that seals the bag opening; a solution filling/discharge port through the plug; a cup-shaped, thermoformed sleeve (13) that fits partly about the bag and is made from a dispersion of an osmotically effective solute in a water soluble, thermoplastic polymer vehicle; a shape-retaining, semipermeable membrane (12) that encapulates the bag-sleeve subassembly; and a flow moderator (28) that is received through the filling/discharge port in the plug. <IMAGE>
Description
SPECIFICATION
Osmotically Driven Fluid Dispenser
The invention relates to improvements and modifications of an osmotically driven fluid dispenser and is an improvement in the osmotically driven dispensers described in commonly owned U.S. Patent No. 3,987,790,
U.S. Patent No. 3,995,631 and U.S. Patent No.
4,034,756. Therefore, these patents are believed to be relevant prior art, particularly the minipump described in these patents. The minipump's components are an inner flexible bag that holds the drug charge, an intermediate layer of an osmotically effective solute composition, such as an inorganic salt, that encapsulates the bag, an outer shape-retaining membrane that is at least in part permeable to water and that encapsulates both the layer of osmotically effective solute composition and the bag, a plug that seals the open end of the bag, and a filling/discharge port that communicates with the interior of the bag.
In operation the bag is filled with drug solution via the filling/discharge port and placed in an aqueous environment, such as body cavity or within body tissue. Water is imbibed from the environment by the osmotically effective solute through the membrane into the space between the inner flexible bag and the membrane. Since the bag is-flexible#and the membrane is rigid, the imbibed water squeezes the bag inwardly, thereby displacing drug out the filling/discharge port.
Minipumps of the above described structure and operation perform well but are not beyond being improved. Two shortcomings of the minipump are: 1. the layer of osmotically effective solute is applied by dipping the inner bag into a suspension of an osmotically active solute, which is a highly labor intensive process, and 2. uniformity and reliability of the thickness of the solute layer are difficult to assure in large scale production due to the inherent variability of the dipping process. The first shortcoming affects the ease and cost of production. The second shortcoming affects the average release rate of drug, the constancy of the release rate, and the duration of release.
According to the present invention, there is provided an osmotically driven fluid dispenser comprising an inner flexible bag adapted to
contain the fluid, an intermediate layer of an osmotically effective solute composition at least
partly encapsulating the bag, an outer, shape
retaining membrane encapsulating the layer of
osmotically effective solute composition, said
membrane being at least in part permeable to water, and a port that extends from the interior of the bag to the exterior of the dispenser through which the fluid may be charged into the bag and
dispensed from the bag, characterised in that the
layer of the osmotically effective solute
composition is in the form of a thermoformed
sleeve comprising a dispersion of 50% to 75% by
weight osmotically effective solute in 25% to 50%
by weight water soluble thermoplastic polymer
vehicle.
Following is a description by way of example
only and with reference to the accompanying
drawings of methods of carrying the invention
into effect.
In the drawings~ Figure 1 is an elevational, exploded, sectional
view of one embodiment of the dispenser of the
invention;
Figure 2 is an enlarged sectional view of the
dispenser of Figure 1; and
Figure 3 is a sectional view of the dispenser for
Figure 1 taken along the line 3-3 of Figure 2.
Like numerals refer to like parts in the various
figures.
The drawings illustrate an osmotically driven
fluid dispenser, generally designated 11. As
shown in Figure 1, the basic components of
dispenser 11 are an outer, shape-retaining
semipermeable membrane 12, an intermediate
thermoformed sleeve 13 made from a dispersion
of an osmotically effective solute in a water
soluble, theremoplastic polymer vehicle (matrix),
an inner flexible bag 14, a plug 1 5, a flow
moderator 16, and a flow moderator cap 17.
Bag 14 is adapted to contain a fluid
composition such as an active agent composition
18 (Figure 2) in fluid form. The term "active
agent" as used herein means any compound or
mixture of compounds that can be dispensed to
produce a predetermined beneficial and useful
result. Active agents include pesticides,
germicides, biocides, algicides, rodenticides,
fungicides, insecticides, antioxidants, plant
growth promoters, plant growth inhibitors,
preserving agents, surfactants, disinfectants,
sterilization agents, catalysts, chemical reactants,
fermentation agents, cosmetics, foods, nutrients,
food supplements, drugs, vitamins, sex sterilants,
fertility inhibitors, fertility promoters, air purifiers,
micro-organism attenuators, and other
compositions that benefit the environment,
surroundings and habitat, including animals and
humans.In the preferred embodiment the active
agent is a drug that produces a local or systemic
physiologic or pharmacologic response when
adminstered to animals or humans.
In order to be a suitable container for the fluid,
bag 14 should be substantially impermeable to
the fluid composition and be compatible with the
composition. By "compatible", it is meant that the
bag should not be corroded, solubilized, or
otherwise affected deleteriously by the ;composition. Additionally, when the composition
is a drug, the composition should# not be
significantly contaminated by the bag, such as by
the extraction of leachables from the material
forming the bag. Bag 14 may be made from
elastomeric compositions that may be formed
into thin sheets. The elastomeric properties of the
elastomeric composition and the thickness of the
bag wall should be such as to cause the bag to
readily collapse inwardly when a force is applied
to the bag exterior. Such elastorneric compositions are disclosed in commonly owned
U.S.Patent No. 3,760,984 at col. 5, line 40 to col. 7, line 37 and in commonly owned U.S.
Patent No. 3,995,631 atcol. 8, lines 14-32 which disclosures are incorporated herein by reference.
Bag 14 is elongated and generally cylindrical and is closed at its end 19 and open at its opposite end 22. Its wall is thickened outwardly at 23 to form a shoulder 24. As seen in Figure 2 the portion of the exterior of bag 14 below shoulder 24 is encapsulated by sleeve 13 whose wall is approximately as thick as shoulder 24 is wide.
Sleeve 13 is made from a thermoformabie osrnotically effective solute composition. The components of the composition are an osmotically effective solute and a water soluble, theremoplastic polymer vehicle. The purpose of the solute is to imbibe water from the environment across membrane 12 into the space between the exterior of bag 14 and the inner surface of membrane 12, that is, the space occupied by sleeve 13.
The osmotic pressure of the solute when in solution should be significantly greater than the osmotic pressure of the liquid of the environment.
In dispensers that are to be ingested by or placed within an animal, the osmotic pressure of the solution must exceed the osmotic pressure of the body fluids (about 750 kPa). Osmotically effective solutes that may be used in sleeve 13 are disclosed in U.S. Patent No. 3,760,984 at col. 7, line 38 to col. 8, line 2 and in U.S. Patent No.
3,995,631 at p. 1 line 65 to col. 12, line 3 and col. 14, lines 20-28, which disclosures are incorporated herein by reference. Sodium chloride is an especially effective osmotic solute in that the osmotic pressure of sodium chloride is sufficiently high to remove the dependence of pumping rate on the osmotic pressure of the surrounding environment. Sodium chloride is efficient in salting out the polymer vehicle so that the influence of binder does not enter into the performance of the dispenser, and the dispenser
is less imposing than those containing other salts on the surrounding biological environment.
The polymer vehicle serves to make the osmotically effective composition thermoformable. Depending upon its osmotic pressure in solution it may also contribute to the osmotic effectiveness of the composition. The vehicle functions as a matrix in which the osmotically effective solute is dispersed, and renders the composition flowable upon application of heat and pressure. A preferred vehicle is a mixture of 40% to 70% by weight poly(ethylene oxide) having a molecular weight in the range of 100,000 to 4,000,000 and 30% to 60% by weight poly(ethylene glycol) having a molecular weight in the range of 1,000 and 30,000,
The thermoformability of the composition permits sleeve 13 to be produced by conventional
thermoforming techniques such as compression molding, injection molding, or extrusion.Because of this, sleeve 13 may be made as a module in large quantities with a high degree of thickness reproducibility. With sleeve 13 in modular form the ass#embly of dispenser 1 1 is simplified.
Furthermore, the subassembly composed of bag 14 and sleeve 13 is not as fragile as the solute coated bags of prior versions of the minipump.
Thus the subassemblies are less likely to be damaged in the coating process by which membrane 12 is applied to the subassembly.
In addition to the solute and vehicle the osmotically effective solute composition may contain minor amounts of other materials such as fillers, pigments, lubricants, and other conventional additives that facilitate thermoforming.
Sleeve 13 is encapsulated by outer membrane 12. Membrane 12 also covers the exterior of the portion of bag 14 above shoulder 24 and forms a fluid tight seal therewith. At least a part of membrane 12 is permeable to water. Membrane 12 is impermeable to the osmotically effective solute composition. Membrane 12 is also shaperetaining, that is, it is sufficiently rigid to be substantially underformed by the hydrostatic pressure that is generated in the space between its inner surface and the exterior of bag 14 by the water imbibed by the solute of sleeve 13. The thickness and composition of membrane 12 affect the rate at which water will be imbibed through it by the solute in sleeve 13.Such membranes and compositions that may be used to form them include cellulose acetates, cellulose acetate butyrates, and other shape-retaining semipermeable membranes including those disclosed in said U.S. Patent No. 3,760,984 at col.4, line 53 to col. 5, line 39 and in said U.S.
Patent No. 3,995,631 at col. 7, line 40 to col. 8, line 15, which disclosures are incorporated herein by reference.
Plug 15 fits into the open end 22 of bag 14.
Plug 15 is generally cylindrical and is approximately as long as the thickened portion of
bag 14 above shoulder 24. The exterior of plug 1 5 forms a fluid tight seal with the portion of interior surface of bag 14 with which it is in contact. Plug
15 has an axial, central bore 25 extending
completely through it. Bore 25 provides access to the interior of bag 14 for filling bag 14 with active agent composition 18. Bore 25 is also adapted to receive flow moderator 16. Plug 15 has a hemispherically shaped recess 26 in its inner (bottom) end 27. The presence of such a recess or concavity in end 27 reduces the likelihood of entrapping air in bag 14 when filling bag 14 with composition 18. In prior versions of the minipump this plug has been generally cylindrical in shape, its inner end joining the wall of the bag at a 900 angle. During the filling of the bag, the fluid has a natural tendency, due to its high surface tension, to form a curved surface beginning near the top of the wall of the bag and continuing up to the filling/discharge port. This curvature causes an air pocket at the intersection of the wall of the bag and the plug. Plug 15 has a hemispherically recessed lower surface, curved to substantially match the arc created by the surface tension of the drug solution during the filling process. This configuration reduces the volume of the dispenser which cannot be filled due to air entrapment from approximately 1 5% to less than 2% to 3%. Plug 15 may be made from the same materials as are used to make flexible bag 14; however, the dimensions of plug 15 should be such that it is substantially inflexible.
Flow moderator 16 provides the passageway from the interior of bag 14 to the exterior of dispenser 11 by which composition 18 is discharged from dispenser 11. Flow moderator 16 comprises a conduit, in the form of a rigid cylindrical tube 28, and a dome-shaped head 29.
Tube 24 and head 29 may be made from suitable plastics or metals. Head 29 has an axial, threaded bore 32 that receives threaded end 33 of tube 28.
As shown in Figures 1 and 2, end 33 extends outwardly from the spherical surface of head 29 to provide a site for attaching an external catheter tube (not shown) in the event dispenser 11 is to be used to administer composition 18 to a remote location. The outer diameter of tube 28 is approximately the same as the diameter of bore 25 such that tube 28 may be inserted through bore 25 into bag 14 with tube 28 fitting snugly within bore 25 so as to form an essentially fluid tight seal with plug 15. The length of tube 28 is such that it extends into bag 14 to at least about 50% of the elongated dimension of the interior of bag 14, i.e., the distance from the inner side of end 19 to end 27 of plug 15. Preferably tube 28 extends into bag 14 over substantially the entire, but not all of (say 85% to 95%), of said elongated dimension.The inner diameter of tube 28 is correlated to the length of tube 28 such that substantial diffusional flow of composition, 18 through tube 28 will not occur. Tube 28 is, in effect, a capillary that provides resistance to the flow of composition 18, thereby reducing or eliminating bulk loss of composition 18, from the outlet port of dispenser 11. Head 29 has a diameter slightly less than the outer diameter of plug 15. As seen in Figure 2, the flat side of head 29 fits against the top of plug 15.
Dispenser 11 may be filled with fluid 18 via bore 25 of plug 15. For instance, the needle of a fluid loaded syringe may be inserted through bore 25 and the syringe's contents discharged into bag 14. To insure that a predetermined fluid pumping rate is achieved, it is desirable to completely fill bag 14 with fluid 18. After the bag is filled, tube 28 of flow moderator 16 is inserted through bore 25 to the position shown in Figure 2. As described above, tube 28 functions as a capillary and inhibits loss of fluid 1 8 from the dispenser even though it is subjected to substantial movement or tipped upside down. Dispenser 11 operates in the following manner.Once placed in aqueous environment, such as within a body cavity or within body tissue, water from the environment is imbibed by the solute of sleeve 13 through membrane 12 at a rate determined by the osmotic activity of the solute, and the osmotic reflection coefficient, composition, thickness, and area of membrane 12. The imbibed water causes the volume of the space between the inner surface of membrane 12 and the exterior of bag 14 (the space initially occupied by sleeve 13) to increase. And since membrane 12 is shaperetaining, the imbibed water generates hydraulic pressure on the exterior of bag 14 causing bag 14 to be squeezed inwardly. This squeezing forces fluid 18 through tube 28 and out of the dispenser.
As indicated, fluid 18 may be an active agent composition. In such instances the dispenser 11 will, of course, discharge active agent directly.
Alternatively, fluid 18 may be inert and the dispenser may be used simply as a displacement
pump. In this alternative the dispenser will, of course, have to be suitably interconnected by well known means to a reservoir of the fluid (active agent) to be discharged, such that the inert fluid displaces the fluid from the reservoir in a predetermined regimen to the desired
administration site. Such alternatives are
particularly attractive in instances in which the fluid to be discharged is incompatible with bag
14.
Flow moderator cap 17 may be used to cover protruding end 33 of tube 29 when dispenser 11
is used without an external catheter tube connection. Cap 17 is cresent-shaped and has an
axial threaded bore 34 that receives end 33 of tube 29. The curvature of its concave underside
35 matches the convexity of the top surface of
head 29 so that the former fits tightly against the
latter (Figure 2). The outer diameter of cap 17 is the same as the outer diameter of membrane 12.
Thus the hemispherical exterior of cap 17 provides a smooth blunt surface that aligns with the exterior surface of membrane 12.
The components of dispenser 11 may be made and assembled as follows. Bag 14 and sleeve 13 are thermoformed, such as by injection molding, by known techniques. The bag-sleeve subassembly may be made using solvent or adhesive bonding, depending on the material involved. If bag 14 and sleeve 13 are capable of being solvent bonded, bag 14 is dipped in the mutual solvent and inserted into sleeve 13. When the subassembly is put together by adhesive bonding, bag 14 is dipped into an appropriate adhesive and then inserted into sleeve 13.
Membrane 12 may be applied to the bag-sleeve subassembly by dipping it in a solution of membrane material as taught in U.S. Patent No.
3,987,790 at col, 4, line 63 or membrane 12 may be coated onto the subassembly using conventional coating equipment and techniques such as pan coating and fluidized spray coating.
The following example is intended to further illustrate the above described dispenser and its manufacture. This example is not intended to limit the invention in any way.
Example
Cylindrical flexible bags (2.50 cm long, 4.01 mm I.D. and 4.62 mm O.D.) were injection molded at 1 760C, 3.5x 103 kPa, from an elastomeric styrene-butadiene copolymer (sold under the trade designation, Kraton 2104).
Osmotic sleeves were prepared for each dispenser as follows. The components (64.5wt% NaC1, 20 wt%poly[ethylene oxide], molecular wt 600,000, 1 5 \not% poly[ethylene glycol ] of molecular weight 20,000 and 0.5 wt% colloidal
SiO2, sold under the trade name Cabosil) were bulk blended in a Hobart mixer for 20 minutes at low speed. The homogenous powder blend-was pressed into 0.6 cm tablets capable of being gravity fed into Arborg injection molding equipment. The osmotic sleeves (2.21 cm long, 4.87 mm l.D and 5.89 mm O.D.) were formed from the tablets by injection molding at 1 49 OC, 6.5x 103 kPa.
Cylindrical plugs of the above described styrenebutadiene copolymer were injection molded. The plugs were 0.5 cm long, had a 4.1 mm O.D., and their lower surfaces were recessed hemispherically to a depth of 1.37 mm. Each had a central axial bore 0.76 mm in diameter through its entire length.
The cylindrical flexible bags were dipped into a 1 5 wt% cyclohexane solution of the styrenebutadiene copolymer mentioned above and were inserted into the osmotic sleeve. The arcuate surfaces of the plugs were coated with a glue bead of 15 wt% cyclohexane solution of the copolymer and a plug was inserted into the open end of each of the bags. A 22 gauge needle was inserted through the bore of each plug and the plugged bags were placed in an oven at 400C for 2 hours.
An outer semipermeable membrane was applied to the dispensers by coating with a
Wurster coater. The membrane was a 4 wt% methylene chloride solution of cellulose acetate butyrate (sold under the designation Eastman
Kodak 381-2). The coating was applied to a thickness of 0.38 mm. The dispensers were then oven-dried at 550C for about 5-10 days.
Flow moderators were prepared for each dispenser as follows. Twenty-one gauge needle stock was cut into 2.36 cm lengths. Each length of tubing was circumferentially grooved with 1 5 grooves, equally spaced 0.3 mm apart along one end of the tube, such that a 4.3 mm distance beginning at one end of the tube is grooved. Caps were inserted around the grooved portion of the tube 3 mm from the grooved end, from styreneacrylonitrile copolymer. The caps were hemispherical, 5.6 mm in diameter, with a 0.8 mm diameter diametrical bore. Hemispherical overcaps had a 6.5 mm O.D., were 4.3 mm in length with the bottom hemispherically recessed to a depth of 1.3 mm, had a 0.8 mm diameter diametrical bore through the length of the overcap, and were injection molded from ethylene-vinyl-acetate copolymer. The overcaps were pressed onto the 3 mm grooved extension of the tube.
Claims (5)
1. An osmotically driven fluid dispenser comprising an inner flexible bag adapted to contain the fluid, an intermediate layer of an osmotically effective solute composition at least partly encapsulating the bag, an outer, shaperetaining membrane encapsulating the layer of osmotically effective solute composition, said membrane being at least in part permeable to water, and a port that extends from the interior of the bag to the exterior of the dispenser through which the fluid may be charged into the bag and dispensed from the bag, characterized in that the layer of the osmotically effective solute composition is in the form of a thermoformed sleeve comprising a dispersion of 50% to 75% by weight osmotically effective solute, in 25% to 50% by weight water soluble thermoplastic polymer vehicle.
2. A dispenser as claimed in claim 1 wherein the osmotically effective solute constitutes 60% to 70% by weight of the dispersion and the polymer vehicle constitutes 30% to 40% by weight of the dispersion.
3. A dispenser as claimed in claim 1 or claim 2 wherein the polymer vehicle comprises 40% to 70% by weight poly(ethylene oxide) having a molecular weight in the range of 100,000 to 4,000,000 and 30% to 60% by weight poly(ethylene glycol) having a molecular weight in the range of 1,000 to 30,000.
4. A dispenser as claimed in any preceding claim wherein the osmotically effective solute is sodium chloride and the vehicle consists of a mixture of poly(ethylene oxide) of approximately 600,000 molecular weight, poly(ethylene glycol) of approximately 20,000 molecular weight, and collodial silicon dioxide.
5. A dispenser as claimed in claim 1 and substantially as herein described with reference to and as illustrated in the accompanying drawings.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3681579A | 1979-05-07 | 1979-05-07 |
Publications (2)
Publication Number | Publication Date |
---|---|
GB2048710A true GB2048710A (en) | 1980-12-17 |
GB2048710B GB2048710B (en) | 1983-03-09 |
Family
ID=21890805
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
GB8011264A Expired GB2048710B (en) | 1979-05-07 | 1980-04-03 | Osmotically driven fluid dispenser |
Country Status (7)
Country | Link |
---|---|
JP (1) | JPS6035170B2 (en) |
CA (1) | CA1142831A (en) |
CH (1) | CH645069A5 (en) |
DE (1) | DE3017342A1 (en) |
FR (1) | FR2455915B1 (en) |
GB (1) | GB2048710B (en) |
IT (1) | IT1131458B (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0048541A1 (en) * | 1980-07-18 | 1982-03-31 | Alza Corporation | Osmotically driven fluid dispenser |
US5830546A (en) * | 1991-10-03 | 1998-11-03 | Holvis Holzstoff S.A. | Reservoir system for prolonged diffusion of an active principle |
GB2391186A (en) * | 2002-05-28 | 2004-02-04 | John Baker | Dosing device using osmosis to generate internal pressure to expel dosing product |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0268207A (en) * | 1988-09-01 | 1990-03-07 | Sumitomo Rubber Ind Ltd | Radial tire for heavy load and high speed |
ZA981610B (en) * | 1997-03-24 | 1999-08-26 | Alza Corp | Self adjustable exit port. |
JP2003521506A (en) * | 2000-02-04 | 2003-07-15 | アルザ・コーポレーション | Osmotically driven liquid dispensers and coating compositions |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1503116A (en) * | 1975-07-28 | 1978-03-08 | Alza Corp | Sustained release drug delivery devices |
US3987790A (en) * | 1975-10-01 | 1976-10-26 | Alza Corporation | Osmotically driven fluid dispenser |
-
1980
- 1980-04-03 GB GB8011264A patent/GB2048710B/en not_active Expired
- 1980-04-15 CA CA000349910A patent/CA1142831A/en not_active Expired
- 1980-05-06 JP JP55059851A patent/JPS6035170B2/en not_active Expired
- 1980-05-06 DE DE19803017342 patent/DE3017342A1/en active Granted
- 1980-05-07 FR FR8010187A patent/FR2455915B1/en not_active Expired
- 1980-05-07 IT IT21875/80A patent/IT1131458B/en active
- 1980-05-07 CH CH357080A patent/CH645069A5/en not_active IP Right Cessation
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0048541A1 (en) * | 1980-07-18 | 1982-03-31 | Alza Corporation | Osmotically driven fluid dispenser |
US5830546A (en) * | 1991-10-03 | 1998-11-03 | Holvis Holzstoff S.A. | Reservoir system for prolonged diffusion of an active principle |
GB2391186A (en) * | 2002-05-28 | 2004-02-04 | John Baker | Dosing device using osmosis to generate internal pressure to expel dosing product |
GB2391186B (en) * | 2002-05-28 | 2004-11-03 | John Baker | Controlled dosing device for toilet flush water or other applications |
Also Published As
Publication number | Publication date |
---|---|
FR2455915B1 (en) | 1988-07-01 |
CH645069A5 (en) | 1984-09-14 |
IT1131458B (en) | 1986-06-25 |
JPS6035170B2 (en) | 1985-08-13 |
CA1142831A (en) | 1983-03-15 |
DE3017342C2 (en) | 1989-05-24 |
IT8021875A0 (en) | 1980-05-07 |
GB2048710B (en) | 1983-03-09 |
DE3017342A1 (en) | 1980-11-27 |
JPS5621603A (en) | 1981-02-28 |
FR2455915A1 (en) | 1980-12-05 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PCNP | Patent ceased through non-payment of renewal fee |
Effective date: 19940403 |