CA1084794A - Osmotically driven active agent dispenser - Google Patents
Osmotically driven active agent dispenserInfo
- Publication number
- CA1084794A CA1084794A CA271,825A CA271825A CA1084794A CA 1084794 A CA1084794 A CA 1084794A CA 271825 A CA271825 A CA 271825A CA 1084794 A CA1084794 A CA 1084794A
- Authority
- CA
- Canada
- Prior art keywords
- wall
- dispenser
- active agent
- water
- passageway
- 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.)
- Expired
Links
Classifications
-
- 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
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
- A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Ophthalmology & Optometry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Preparation (AREA)
- Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
Abstract of the Disclosure Osmotically driven active agents dispenser for use in a water-containing environment that pumps a solution of active agent, such as a drug, at a predetermined, constant rate. The dispenser is in the form of a coated tablet comprising; a core of an osmotically effective active agent composi-tion; and an inexpandable wall that encloses the core, has a controlled permeability to water and has inherent properties, such as brittieness, or sites of structural weakness, that are responsive to the pressure generated within the dispenser by imbibtion of water from the environment by the core through the wall to form at least one, and usually many, passageway in situ in the wall through which the active agent composition in solution is pumped water is being imbibed into the dispenser.
Description
75'4 The invention is a modification o the osmotically driven active '~
agent ~ispenser disclosed in commonly owned Canadian Patent ~pplication No.
173,072 filed June 4, 1973 and the corresponding United States Patent No.
3,845,770, issued November 5, 1974. Briefly, the dispenser o that applica-tion and patent compris~s: a core of an osmotically effective active agent composition; a water insoluble wall that is impermeable to the composition, has a controlled permeability to water and encloses the core; and one or mor~ particularly sized passageways extending through the wall to the core.
When placed in a water-containing environment, such as the gastrointestinal tract, eye~ vagina, and uterus, water is imbibed from the environment by the composition through th~ wall c~using the composition to be dissolved~ a pressure gradient between the interior and exterior of the dispenser to be generated, and the dissolved composition to be pumped out the passageway(s) into the environment. The release of active agent rom these dispensers is continuous, sustained, predetermi~ed, and substantially constant ow r a major portion of the release period. The application discloses that the passage-ways in the wall may be formed mechanically, such as by drilling, or in situ by erosion cf a bioerodible component incorporated into the wall.
The present invention provides an osmotically driven actiYe agent dispenser oT use in a water-containing enYironment comprising a core of an osmotically efective active agent composition, a wall enclosing the core that is substantially inexpandable, substantially impexm~able to the nctive agent composition, and permeable to water, and an outlet passageway in the wall through which the active agent composition is pumped at a substantially predetermined, substantially constant rate in response to pressure generated within the dispens~r by imbibition of water rom the environment by the core through the wall characterized in that the wall is made o~ a material having ;' a structural weakness that causes the wall to yield under said pressure to form said passageway in situ.
The structural weakness of the wall material ma~ be an inherent property of'the'wall material, or it may be proviaed by sites of structural ~eakness incorporated in the material.
, , .. . ~ .
1~4~5~4 The drawing is a graph of the active agent release pattern of the dispensers of the example sct forth belowO The graph plots release rate versus time.
As indicated above, the dispenser of this invention is a unique modification of the dispenser of Canadian application number 173,072 filed June 4, 1973, and United States Patent 3,845,770, issued November 5, 1974~
The difference between the dispenser of said application and patent and ~he present dispenser is that the present dispenser does not have a pre~
formed passageway or a bioerodible wall component that erodes in situ to form a passageway, but instead its wall is made of a material having inherent properties or sites of structural weakness that cause the wall yield under the osmotically generated pressure within the dispenser to form at least one and usually many passageways in situ in the wall. These passageways serve the same function as the preformed or in situ erosion formed passageway of the dispenser of said Canadian patent application number 173,072 and United States Patent 3,845,770.
The terms ~'aqueous environment", "active agent", "drug", "osmotically effective", and "wall" used herein have generally the same meanings as in Canadian patent application number 173,072.
Al90, the form and utility of the invention dispenser may be the same as that of the dispenser of said application and patent and the reader is directed to the appropriate portions of the disclosure of said application, or patent for particulars in this regard. Likewise, the materials that are used to form the wall, the characteristics (except for the abovenoted inherent properties and sites of structural weakness) of the wall, and the procedures used to form the core and enclose it within the wall may be the same as those of said application and patent and the reader is directed to the disclosures thereof for further information relevant to these items.
As in the dispenser of said application and patent, the active agent _ 2 -'` ;.~
-` I0~75~
composition that forms the core of the invention dispenser is an osmotically effect:ive solute. In this regard the composition may be agent that itself is such a solute and that is neat or formulated with a carrier that may or may not also be such a solute, or agent that is not such a solute ~ormulated with a carrier, that is such a solute. In its osmotically effective solute role, the composition imbibes water from the environment inwardly through the wall of the dispenser. The imbibed water dissolves the composition and a hydro-static pressure difference is established across the wall between the solution of active agent composition and the aqueous environment. The magnitude of and the rate of generation of this difference will depend upon the solubility of the composition in water, the number of ionic species it produces in solution, and the concentration ~radient across the wall. The difference must be sufficient to cause the wall to yield and form the passageway(s). Once the passageways are thus formed, water is imbibed continuously into the dispenser in response to the osmotic pressure gradient across the wall. The imbibed water in turn continuously forces the solution of composition out the passage-way(s) into the environment. Accordingly the solute should generate a significantly higher osmotic pressure in solution than the osmotic pressure of the aqueous environment in which the dispenser is used. For instance in embodiments that release drugs into body fluids solutes that exhibit a signif-:icantly higher osmotic pressure than such fluids ti.e. significantly higher than about 750 kPa) must be used. Solutes that exhibit osmotic pressures in -the range of about 20,000 to about 40,000 kPa will normally be used in such drug dispensing embodiments. Osmotic pressure may be measured with a commercially available osmometer that measures the vapor pressure difference ;
between pure water and the composition solution. The vapor pressure ratio may be converted into osmotic pressure difference by standard thermodynamic calculations.
The wall of the present dispenser is substantially inexpandable as :~ :
~.1)8~L7~3~
is the wall of the said application and patent dispenser. This means that there is no substantial increase in the volume of the core before or during the dispensing period despite imbibition of water.
The sites of structural weakness in the wall that cause it to yield under pressure may be caused by: incorporating foreign materials, e.g., fillers, in the polymer forming the wall; using a blend of incompatible poly-mers to make the wall; or, depending on the wall material, post-treating the wall thermally, by solvent crazing, or by irradiation. Inherent properties of the wall material that cause it to yield under pressure may be the brittle-ness of the material, may be a result of the composition of the wall (such asin the case of a polymer its crystallinity, molecular weight, degree and nature of cross-linking, and the presence and structure of side groups on the polymer backbone) and/or may be a result ofthemanner in which the wall is formed.
The passageways formed as a result of the wall yielding will gener-ally be irregularly shaped, sized, and positioned and may in the form of discrete holes or a network of cracks or fissures extending over part or all of the dispenser surface. Individually the passageways are normally minute, usually microscopic, and they constitute an outlet for the solution of active agent that falls within the maximum and minimum si~e limitat:ion9 Aescr:ibed in said application.
In the present dispensers, the ~hickness of the wall may affect the passageway formation and in such instances wall thickness will be correlated with the wall properties to insure that one or more passageways meeting the abovementioned minimum/maximum si~e limitations are ~ormed timely. Normally the thickness of the wall will be in the range of about 100 to about 500 microns. ;
Active agent is released from the dispenser as follows. Upon placement of the dispenser in an aqueous environment, water is imbibed through ~
_ 4 - ~;
-~0&~47~
the wall by the core of active agent composition. Since the wall is substan-tially inexpandable the :imbibed water will cause a build up of pressure within the dispenser. During this build up there is no release of composition by osmotic pumping. The pressure builds up until it is sufficient to cause the wall to yield to form the passageway. For instance if the brittleness of the wall causes such yielding, the pressure has built up to the point at which brittle failure is initiated and the wall cracks. In instances in which there are sites of structural weakness in the wall the pressure has built up to the point at which stress fracture occurs at such a site or sites. The magnitude of this threshold pressure will vary with the particular properties or kinds of sites involved and the thickness of the wall. Desirably it will be relatively low, that is in the range of about 50 to about 5000 kPa. Once the passageway~s) is/are formed the pressure is relieved and osmotic pumping of the solution begins. After a short period of time, steady state conditions are reached and the solution of active agent composition is being pumped out of thF in situ-formed passageway(s) at a substantially constant rate. The magnitude of the constant rate is dependent primarily upon the rate of water imbibition into the dispenser and is independent of the si3e of the passage-way(s), provided such size is within the abovedescribed maximum/minimum size limitations. This substantially constant rate prevails over ~e major portion of the dispensing period. A~ter the active agent composition has been depleted to the extent that a saturated solution of composition is not main-tained within the dispenser, the rate of release decreases as the concentra-tion of active agent in solution within the dispenser decreases.
E2~A~I.E .
The following example illustrates an embodiment of the in~ention that may be used to dispense the drug potassium chloride. This example is not intended to limit the invention in any manner. Unless indicated otherwise, percentages are by weight.
7~
Corcs of potassium chloride containing 5% FD&C Blue #l water sol-uble dye in the form of compressed tablets were m~de using a Manesty rotary tableting machine with 0.95 cm diame~er standard concave punches set to a hardness of 8 kg. A n~xture of cellulose acetate (sold by ~astman Kodak under the designation E-320) of 32% acetyl content and the water insoluble aluminum lake dye, FD~C Yellow #5 in a 99:1 weight ratio was made up as a 5%
solution in acetone/water (88.5%/11.5%)~ This solution was deposited on the potassium chloride cores using a Wurs~er air suspension apparatus to form a 125 micron thick wall or membrane about each core.
The theoretical steady state potassium chloride release rate from the coated tablets was calculated to be ~5 mg/hr, based on a wall surface area of 2.3 cm , a KCl solubility of 360 mg/ml, and a wall water transmission of 0.27 cm mil/cm hr. The formulas appearing in said Canadian patenk application No. 173,072 and United States Patent No. 3,845,770 were used to ;
make these calculations.
Five of the coated tablets were placed in known quantities of water at 37 C. After a short time a passageway/passageways was/were formed in each tablet at a site/sites of structural weakness in the tablet wall caused by the presence of the yellow dye, as evidenced by the appearance of a blue spot/
spots on the walls of the tablet9. Aliquots of the water were taken at one hour intervals beginning 1/2 hour after the tablets were placed in the water.
The KCl content of each aliquot was determined b~ standard KCl analysis techniques~ From these determinations KCl rates from the tablets were calcul~
ated. The average release rate from the five tablets plotted against time is shown in the accompanying drawing. As illustrated in the drawing the in vitro ~ ~-release rate between hours 1 and 9 was substantially constant and corresponded ;~
approximate b with the predicted, theoretical rate. -Modifications of the invention dispenser that are obvious to those skilled in the pharmaceutical and/or chemical arts are intended to be within the scope of the following claims.
agent ~ispenser disclosed in commonly owned Canadian Patent ~pplication No.
173,072 filed June 4, 1973 and the corresponding United States Patent No.
3,845,770, issued November 5, 1974. Briefly, the dispenser o that applica-tion and patent compris~s: a core of an osmotically effective active agent composition; a water insoluble wall that is impermeable to the composition, has a controlled permeability to water and encloses the core; and one or mor~ particularly sized passageways extending through the wall to the core.
When placed in a water-containing environment, such as the gastrointestinal tract, eye~ vagina, and uterus, water is imbibed from the environment by the composition through th~ wall c~using the composition to be dissolved~ a pressure gradient between the interior and exterior of the dispenser to be generated, and the dissolved composition to be pumped out the passageway(s) into the environment. The release of active agent rom these dispensers is continuous, sustained, predetermi~ed, and substantially constant ow r a major portion of the release period. The application discloses that the passage-ways in the wall may be formed mechanically, such as by drilling, or in situ by erosion cf a bioerodible component incorporated into the wall.
The present invention provides an osmotically driven actiYe agent dispenser oT use in a water-containing enYironment comprising a core of an osmotically efective active agent composition, a wall enclosing the core that is substantially inexpandable, substantially impexm~able to the nctive agent composition, and permeable to water, and an outlet passageway in the wall through which the active agent composition is pumped at a substantially predetermined, substantially constant rate in response to pressure generated within the dispens~r by imbibition of water rom the environment by the core through the wall characterized in that the wall is made o~ a material having ;' a structural weakness that causes the wall to yield under said pressure to form said passageway in situ.
The structural weakness of the wall material ma~ be an inherent property of'the'wall material, or it may be proviaed by sites of structural ~eakness incorporated in the material.
, , .. . ~ .
1~4~5~4 The drawing is a graph of the active agent release pattern of the dispensers of the example sct forth belowO The graph plots release rate versus time.
As indicated above, the dispenser of this invention is a unique modification of the dispenser of Canadian application number 173,072 filed June 4, 1973, and United States Patent 3,845,770, issued November 5, 1974~
The difference between the dispenser of said application and patent and ~he present dispenser is that the present dispenser does not have a pre~
formed passageway or a bioerodible wall component that erodes in situ to form a passageway, but instead its wall is made of a material having inherent properties or sites of structural weakness that cause the wall yield under the osmotically generated pressure within the dispenser to form at least one and usually many passageways in situ in the wall. These passageways serve the same function as the preformed or in situ erosion formed passageway of the dispenser of said Canadian patent application number 173,072 and United States Patent 3,845,770.
The terms ~'aqueous environment", "active agent", "drug", "osmotically effective", and "wall" used herein have generally the same meanings as in Canadian patent application number 173,072.
Al90, the form and utility of the invention dispenser may be the same as that of the dispenser of said application and patent and the reader is directed to the appropriate portions of the disclosure of said application, or patent for particulars in this regard. Likewise, the materials that are used to form the wall, the characteristics (except for the abovenoted inherent properties and sites of structural weakness) of the wall, and the procedures used to form the core and enclose it within the wall may be the same as those of said application and patent and the reader is directed to the disclosures thereof for further information relevant to these items.
As in the dispenser of said application and patent, the active agent _ 2 -'` ;.~
-` I0~75~
composition that forms the core of the invention dispenser is an osmotically effect:ive solute. In this regard the composition may be agent that itself is such a solute and that is neat or formulated with a carrier that may or may not also be such a solute, or agent that is not such a solute ~ormulated with a carrier, that is such a solute. In its osmotically effective solute role, the composition imbibes water from the environment inwardly through the wall of the dispenser. The imbibed water dissolves the composition and a hydro-static pressure difference is established across the wall between the solution of active agent composition and the aqueous environment. The magnitude of and the rate of generation of this difference will depend upon the solubility of the composition in water, the number of ionic species it produces in solution, and the concentration ~radient across the wall. The difference must be sufficient to cause the wall to yield and form the passageway(s). Once the passageways are thus formed, water is imbibed continuously into the dispenser in response to the osmotic pressure gradient across the wall. The imbibed water in turn continuously forces the solution of composition out the passage-way(s) into the environment. Accordingly the solute should generate a significantly higher osmotic pressure in solution than the osmotic pressure of the aqueous environment in which the dispenser is used. For instance in embodiments that release drugs into body fluids solutes that exhibit a signif-:icantly higher osmotic pressure than such fluids ti.e. significantly higher than about 750 kPa) must be used. Solutes that exhibit osmotic pressures in -the range of about 20,000 to about 40,000 kPa will normally be used in such drug dispensing embodiments. Osmotic pressure may be measured with a commercially available osmometer that measures the vapor pressure difference ;
between pure water and the composition solution. The vapor pressure ratio may be converted into osmotic pressure difference by standard thermodynamic calculations.
The wall of the present dispenser is substantially inexpandable as :~ :
~.1)8~L7~3~
is the wall of the said application and patent dispenser. This means that there is no substantial increase in the volume of the core before or during the dispensing period despite imbibition of water.
The sites of structural weakness in the wall that cause it to yield under pressure may be caused by: incorporating foreign materials, e.g., fillers, in the polymer forming the wall; using a blend of incompatible poly-mers to make the wall; or, depending on the wall material, post-treating the wall thermally, by solvent crazing, or by irradiation. Inherent properties of the wall material that cause it to yield under pressure may be the brittle-ness of the material, may be a result of the composition of the wall (such asin the case of a polymer its crystallinity, molecular weight, degree and nature of cross-linking, and the presence and structure of side groups on the polymer backbone) and/or may be a result ofthemanner in which the wall is formed.
The passageways formed as a result of the wall yielding will gener-ally be irregularly shaped, sized, and positioned and may in the form of discrete holes or a network of cracks or fissures extending over part or all of the dispenser surface. Individually the passageways are normally minute, usually microscopic, and they constitute an outlet for the solution of active agent that falls within the maximum and minimum si~e limitat:ion9 Aescr:ibed in said application.
In the present dispensers, the ~hickness of the wall may affect the passageway formation and in such instances wall thickness will be correlated with the wall properties to insure that one or more passageways meeting the abovementioned minimum/maximum si~e limitations are ~ormed timely. Normally the thickness of the wall will be in the range of about 100 to about 500 microns. ;
Active agent is released from the dispenser as follows. Upon placement of the dispenser in an aqueous environment, water is imbibed through ~
_ 4 - ~;
-~0&~47~
the wall by the core of active agent composition. Since the wall is substan-tially inexpandable the :imbibed water will cause a build up of pressure within the dispenser. During this build up there is no release of composition by osmotic pumping. The pressure builds up until it is sufficient to cause the wall to yield to form the passageway. For instance if the brittleness of the wall causes such yielding, the pressure has built up to the point at which brittle failure is initiated and the wall cracks. In instances in which there are sites of structural weakness in the wall the pressure has built up to the point at which stress fracture occurs at such a site or sites. The magnitude of this threshold pressure will vary with the particular properties or kinds of sites involved and the thickness of the wall. Desirably it will be relatively low, that is in the range of about 50 to about 5000 kPa. Once the passageway~s) is/are formed the pressure is relieved and osmotic pumping of the solution begins. After a short period of time, steady state conditions are reached and the solution of active agent composition is being pumped out of thF in situ-formed passageway(s) at a substantially constant rate. The magnitude of the constant rate is dependent primarily upon the rate of water imbibition into the dispenser and is independent of the si3e of the passage-way(s), provided such size is within the abovedescribed maximum/minimum size limitations. This substantially constant rate prevails over ~e major portion of the dispensing period. A~ter the active agent composition has been depleted to the extent that a saturated solution of composition is not main-tained within the dispenser, the rate of release decreases as the concentra-tion of active agent in solution within the dispenser decreases.
E2~A~I.E .
The following example illustrates an embodiment of the in~ention that may be used to dispense the drug potassium chloride. This example is not intended to limit the invention in any manner. Unless indicated otherwise, percentages are by weight.
7~
Corcs of potassium chloride containing 5% FD&C Blue #l water sol-uble dye in the form of compressed tablets were m~de using a Manesty rotary tableting machine with 0.95 cm diame~er standard concave punches set to a hardness of 8 kg. A n~xture of cellulose acetate (sold by ~astman Kodak under the designation E-320) of 32% acetyl content and the water insoluble aluminum lake dye, FD~C Yellow #5 in a 99:1 weight ratio was made up as a 5%
solution in acetone/water (88.5%/11.5%)~ This solution was deposited on the potassium chloride cores using a Wurs~er air suspension apparatus to form a 125 micron thick wall or membrane about each core.
The theoretical steady state potassium chloride release rate from the coated tablets was calculated to be ~5 mg/hr, based on a wall surface area of 2.3 cm , a KCl solubility of 360 mg/ml, and a wall water transmission of 0.27 cm mil/cm hr. The formulas appearing in said Canadian patenk application No. 173,072 and United States Patent No. 3,845,770 were used to ;
make these calculations.
Five of the coated tablets were placed in known quantities of water at 37 C. After a short time a passageway/passageways was/were formed in each tablet at a site/sites of structural weakness in the tablet wall caused by the presence of the yellow dye, as evidenced by the appearance of a blue spot/
spots on the walls of the tablet9. Aliquots of the water were taken at one hour intervals beginning 1/2 hour after the tablets were placed in the water.
The KCl content of each aliquot was determined b~ standard KCl analysis techniques~ From these determinations KCl rates from the tablets were calcul~
ated. The average release rate from the five tablets plotted against time is shown in the accompanying drawing. As illustrated in the drawing the in vitro ~ ~-release rate between hours 1 and 9 was substantially constant and corresponded ;~
approximate b with the predicted, theoretical rate. -Modifications of the invention dispenser that are obvious to those skilled in the pharmaceutical and/or chemical arts are intended to be within the scope of the following claims.
Claims (8)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. An osmotically driven active agent dispenser for use in a water-containing environment comprising a core of an osmotically effective active agent composition, a wall enclosing the core that is substantially inexpand-able, substantially impermeable to the active agent composition, and permeable to water, and an outlet passageway in the wall through which the active agent composition is pumped at a substantially predetermined, substantially con-stant rate in response to pressure generated within the dispenser by im-bibition of water from the environment by the core through the wall characterized in that the wall is made of a material having a structural weakness that causes the wall to yield under said pressure to form said passageway in situ.
2. The dispenser of claim 1 further characterized in that the wall is made of a material having inherent properties of structural weakness.
3. The dispenser of claim 1 further characterized in that the wall is made of a material having sites of structural weakness.
4. The dispenser of claim 1, 2 or 3 further characterized in that the active agent is a drug.
5. The dispenser of claim 3 further characterized in that the sites of structural weakness are the result of incorporating a foreign material into the material forming the wall, forming the wall from mutually in-compatible polymers, treating the wall thermally, solvent crazing the wall, or subjecting the wall to irradiation.
6. The dispenser of claim 1, 2 or 3 further characterized in that said yielding forms more than one passageway and the passageways are irregularly shaped, sized and positioned.
7. The dispenser of claim 1, 2 or 3 further characterized in that the passageway is in the forms of a network of cracks extending over at least a part of the surface of the dispenser.
8. The dispenser of claim 1, 2 or 3 further characterized in that the passageway is in the form of a plurality of discrete holes.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/663,665 US4016880A (en) | 1976-03-04 | 1976-03-04 | Osmotically driven active agent dispenser |
| US663,665 | 1976-03-04 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1084794A true CA1084794A (en) | 1980-09-02 |
Family
ID=24662802
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA271,825A Expired CA1084794A (en) | 1976-03-04 | 1977-02-15 | Osmotically driven active agent dispenser |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4016880A (en) |
| JP (1) | JPS52106379A (en) |
| AU (1) | AU505303B2 (en) |
| CA (1) | CA1084794A (en) |
| CH (1) | CH616079A5 (en) |
| DE (1) | DE2709356C2 (en) |
| FR (1) | FR2342764A1 (en) |
| GB (1) | GB1527452A (en) |
| IE (1) | IE44787B1 (en) |
| IT (1) | IT1094472B (en) |
| MX (1) | MX145806A (en) |
| SE (1) | SE430302B (en) |
Families Citing this family (130)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2626348C3 (en) * | 1976-06-11 | 1980-01-31 | Siemens Ag, 1000 Berlin Und 8000 Muenchen | Implantable dosing device |
| DE2626294C3 (en) * | 1976-06-11 | 1980-01-10 | Siemens Ag, 1000 Berlin Und 8000 Muenchen | Implantable dosing device |
| US4111201A (en) * | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system for delivering selected beneficial agents having varying degrees of solubility |
| US4111203A (en) * | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system with means for improving delivery kinetics of system |
| US4111202A (en) * | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system for the controlled and delivery of agent over time |
| US4207890A (en) * | 1977-01-04 | 1980-06-17 | Mcneilab, Inc. | Drug-dispensing device and method |
| US4304232A (en) * | 1979-03-14 | 1981-12-08 | Alza Corporation | Unit system having multiplicity of means for dispensing useful agent |
| US4439195A (en) * | 1980-10-14 | 1984-03-27 | Alza Corporation | Theophylline therapy |
| US4484921A (en) * | 1982-02-01 | 1984-11-27 | Alza Corporation | Theophylline therapy utilizing osmotic delivery |
| IE54171B1 (en) * | 1982-06-22 | 1989-07-05 | Univ Glasgow | Device for introducing nutrients and/or therapeutic materials into ruminant animals |
| CA1206049A (en) * | 1982-09-30 | 1986-06-17 | Paul E. Michelson | Osmotic device for physiological applications |
| US4709996A (en) * | 1982-09-30 | 1987-12-01 | Michelson Paul E | Fluid lens |
| US4613330A (en) * | 1982-11-26 | 1986-09-23 | Michelson Paul E | Delivery system for desired agents |
| JPH075457B2 (en) * | 1983-08-16 | 1995-01-25 | ザ ウエルカム フアウンデ−シヨン リミテツド | Pharmaceutical composition allowing the release of the active ingredient in a controlled manner |
| USRE33994E (en) * | 1983-08-16 | 1992-07-14 | Burroughs Wellcome Co. | Pharmaceutical delivery system |
| GB8322007D0 (en) * | 1983-08-16 | 1983-09-21 | Wellcome Found | Pharmaceutical delivery system |
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| US2478182A (en) * | 1945-01-16 | 1949-08-09 | William V Consolazio | Sodium chloride tablet |
| GB972128A (en) * | 1960-01-21 | 1964-10-07 | Wellcome Found | Pellets for supplying biologically active substances to ruminants and the manufacture of such pellets |
| US3247066A (en) * | 1962-09-12 | 1966-04-19 | Parke Davis & Co | Controlled release dosage form containing water-swellable beadlet |
| US3538214A (en) * | 1969-04-22 | 1970-11-03 | Merck & Co Inc | Controlled release medicinal tablets |
| AU466503B2 (en) * | 1972-06-05 | 1975-10-30 | Alza Corporation | Osmotic dispenser |
| US3971376A (en) * | 1973-02-26 | 1976-07-27 | Ceskoslovenska Akademie Ved | Method and apparatus for introducing fluids into the body |
| US3916899A (en) * | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| US3977404A (en) * | 1975-09-08 | 1976-08-31 | Alza Corporation | Osmotic device having microporous reservoir |
-
1976
- 1976-03-04 US US05/663,665 patent/US4016880A/en not_active Expired - Lifetime
-
1977
- 1977-02-01 GB GB4041/77A patent/GB1527452A/en not_active Expired
- 1977-02-08 IE IE266/77A patent/IE44787B1/en not_active IP Right Cessation
- 1977-02-15 CA CA271,825A patent/CA1084794A/en not_active Expired
- 1977-02-23 AU AU22557/77A patent/AU505303B2/en not_active Expired
- 1977-03-01 SE SE7702262A patent/SE430302B/en not_active IP Right Cessation
- 1977-03-03 JP JP2323977A patent/JPS52106379A/en active Granted
- 1977-03-03 CH CH267077A patent/CH616079A5/de not_active IP Right Cessation
- 1977-03-03 IT IT67465/77A patent/IT1094472B/en active
- 1977-03-03 DE DE2709356A patent/DE2709356C2/en not_active Expired
- 1977-03-04 FR FR7706458A patent/FR2342764A1/en active Granted
- 1977-03-04 MX MX168257A patent/MX145806A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US4016880A (en) | 1977-04-12 |
| FR2342764B1 (en) | 1978-10-20 |
| DE2709356A1 (en) | 1977-09-08 |
| SE7702262L (en) | 1977-09-05 |
| US4016880B1 (en) | 1983-02-01 |
| FR2342764A1 (en) | 1977-09-30 |
| JPS52106379A (en) | 1977-09-06 |
| AU505303B2 (en) | 1979-11-15 |
| IE44787L (en) | 1977-09-04 |
| MX145806A (en) | 1982-04-05 |
| IE44787B1 (en) | 1982-04-07 |
| AU2255777A (en) | 1978-08-31 |
| SE430302B (en) | 1983-11-07 |
| IT1094472B (en) | 1985-08-02 |
| JPS6125416B2 (en) | 1986-06-16 |
| CH616079A5 (en) | 1980-03-14 |
| GB1527452A (en) | 1978-10-04 |
| DE2709356C2 (en) | 1985-03-07 |
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