Osmotic device having microporous reservoir

• US 3,977,404 A
• Filed: 09/08/1975
• Issued: 08/31/1976
• Est. Priority Date: 09/08/1975
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Theeuwes, Felix
• Primary Examiner(s): Medbery, Aldrich F.
• Application Number:
  US05/611,504
• Time in Patent Office: 358 Days
• Field of Search: 128/260, 128/130, 128/269, 128/272, 128/127-129, 3/1, 424/19-21, 424/15, 424/37, 222/386.5, 222/389, 222/491, 206/.5
• US Class Current: 424/427
• CPC Class Codes: A61F 6/144 with T-configuration
• CPC Class Codes: A61F 9/0017 implantable in, or in contact with, the eye, e.g. ocular inserts
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

An osmotic device for delivering an active agent is disclosed. The device is comprised of a wall surrounding in at least a part, a reservoir containing agent. The wall is formed of a material permeable to an external fluid and impermeable to agent. The reservoir is formed of a microporous material permeable to agent and fluid, and having at least one micropore that is a passageway for release of agent. The agent is soluble in the fluid and exhibits an osmotic pressure gradient against the fluid, or the agent has limited solubility in the fluid and is admixed with an osmotically effective compound soluble in fluid that exhibits an osmotic pressure gradient against fluid. In operation, agent is released by fluid permeating through the wall into the reservoir producing a solution of agent or a solution of compound containing agent, which solution in either instance is released through the micropore to the exterior of the device.

Claims

1. An osmotic device for the continuous dispensing of an active agent to an environment of use, said device comprising:

a. a shaped wall formed of a semipermeable material that maintains its integrity during the dispensing period and is characterized as permeable to the passage of an external fluid in the environment of use and substantially impermeable to the passage of the active agent with the wall surrounding in at least a part;

b. a reservoir formed of a material having a plurality of micropores with the reservoir containing an active agent that is soluble in the external fluid and exhibits an osmotic pressure gradient across the wall against the fluid;

c. a passageway for dispensing agent from the device, said passageway consisting of at least one micropore that communicates with the reservoir and the exterior of the device; and

d. wherein in operation with the device in the environment of use, external fluid is continuously imbibed through the wall into the reservoir in a tendency towards osmotic equilibrium at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, thereby continuously dissolving the agent which is dispensed from the reservoir through the microporous passageway to the exterior of the device at a controlled rate over a prolonged period of time.

2. The osmotic device according to claim 1 wherein the reservoir is formed of a microporous material having a reflection coefficient of from 0 to 0.5.

3. The osmotic device according to claim 1 wherein the reservoir is formed of a microporous material consisting of from 5 to 95% pores having a pore size of 10 angstroms to 100 microns.

4. The osmotic device according to claim 1 wherein the reservoir is formed of a microporous material consisting of pores with a radius of ##EQU7## wherein J is the volume flux, η

is the viscosity of the liquid, ε

is the porosity, Δ

P is the pressure difference across the material, Δ

x is the thickness of the material and τ

is the tortuosity.

5. The osmotic device according to claim 1 wherein the wall formed of a semipermeable material has a flux consisting of ##EQU8## wherein J is the volume of liquid transported across the wall, A is the area of the wall, h is the thickness of the wall, L_P is the permeability coefficient, σ

is the reflection coefficient, Δ

π

is the osmotic pressure and Δ

P is the hydrostatic pressure.

6. The osmotic device according to claim 1 wherein the active agent is a member selected from the group consisting of levo-dopa, aspirin, salicylamide, ferrous lactate, ferrous fumurate, ferrous gluconate, potassium sulfate, potassium chloride, potassium fluoride, chlorathiazide, acetazolamide, methazolamide, ascorbic acid, benzodiazepines, tolbutamide and chlorpropamide.

7. The osmotic device for the continuous dispensing of an active agent according to claim 1 wherein the reservoir is substantially insoluble in the external fluid and maintains its integrity during the dispensing period.

8. The osmotic device for the continuous dispensing of an active agent according to claim 1 wherein the agent is a member selected from the group consisting of locally and systemically acting drugs and the device is sized and adapted as a dosage form for the administration of agent to the gastrointestinal tract.

9. The osmotic device for the continuous dispensing of an active agent according to claim 1 wherein the agent is mixed with an inorganic or organic osmotically effective compound that exhibits an osmotic pressure gradient against the external fluid.

10. The osmotic device for the continuous dispensing of an active agent according to claim 9 wherein the osmotically effective compound exhibits an osmotic pressure of from 0 to 500 atmospheres.

11. The osmotic device for the continuous dispensing of an active agent according to claim 1 wherein the device is shaped and adapted for vaginal use.

12. The osmotic device for the continuous dispensing of an active agent according to claim 1 wherein the devices is shaped, sized and adapted for placement in the uterus.

13. The osmotic device for the continuous dispensing of an active agent according to claim 12 wherein the agent is a member selected from the group consisting of progestational and estrogenic steroids.

14. The osmotic device for the continuous dispensing of an active agent according to claim 1 wherein the device is structured and adapted to be placed in the anus.

15. The osmotic device for the continuous dispensing of an agent according to claim 1 wherein the semipermeable wall is formed of an erodible material.

16. The osmotic device for the continuous dispensing of an agent according to claim 1 wherein the reservoir is formed of an erodible material.

17. An osmotic device for continuously dispensing an active agent to an environment of use, said device comprising:

a. a shaped wall formed of a semipermeable material that is permeable to the passage of an external fluid and substantially impermeable to the passage of an active agent, said wall surrounding in part;

b. a compartment formed of a microporous material and having at least one micropore that communicates with the compartment and the exterior of the device, said compartment containing an active agent having limited solubility in the external fluid and an osmotically effective compound which exhibits an osmotic pressure gradient across the wall against the fluid;

c. a passageway for dispensing agent from the device, said passageway consisting of at least one micropore that communicates with the exterior of the device; and

d. wherein in operation with the device in the environment of use, external fluid is imbibed through the wall into the compartment in a tendency towards osmotic equilibrium at a rate controlled by the permeability of the wall and the osmotic pressure gradient across the wall thereby continuously dissolving the compound, which as a mixture with the agent, is dispensed through the passageway at a controlled rate for a prolonged period of time.

18. The osmotic device for dispensing an active agent according to claim 17 wherein the agent is a drug.

19. The osmotic device for dispensing an active agent according to claim 17 wherein the osmotically effective compound exhibits an osmotic pressure of from 20 to 500 atmospheres.

20. The osmotic device for dispensing an active agent according to claim 17 wherein the active agent is a member selected from the group consisting of nutrient, vitamin and growth promoter.

21. The osmotic device for dispensing an active agent according to claim 17 wherein the agent is a member selected from the group consisting of biocide, insecticide, fungicide and algicide.

22. An osmotic device for the continuous dispensing of an active agent to an environment of use, said device comprising:

a. a shaped wall formed of a material that is permeable to the passage of an external fluid in the environment of use and substantially impermeable to the passage of an active agent with the wall surrounding;

b. a reservoir formed of a material having a plurality of micropores, said reservoir providing support for the wall and containing an active agent that is soluble in the external fluid and exhibits an osmotic pressure gradient across the wall against the fluid;

c. a passageway for dispensing agent from the device, said passageway consisting of at least one micropore that communicates with the reservoir and the exterior of the device; and

,

d. wherein in operation with the device in the environment of use, external fluid is imbibed through the wall into the reservoir at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, thereby dissolving the agent which is dispensed from the reservoir through the passageway to the exterior of the device at a controlled and continuous rate over time.

23. An ocular osmotic device for the continuous and prolonged administration of an ophthalmic drug, said device comprising:

a. an ophthalmic drug that exhibits an osmotic pressure gradient against eye fluid;

b. a shaped wall formed of a semipermeable material that maintains its integrity during the dispensing period and which material is permeable to the passage of eye fluid and substantially impermeable to the passage of drug, the wall surrounding in part;

c. a reservoir formed of a microporous material with the reservoir containing the drug;

d. a passageway for dispensing the drug from the device, said pasageway consisting of at least one micropore that communicates with the reservoir and the exterior of the device; and

e. wherein in operation with the device in the environment of use, eye fluid is continuously imbibed through the wall into the reservoir in a tendency towards osmotic equilibrium at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall, thereby dissolving the drug which is dispensed from the reservoir through the microporous passageway to the environment at a controlled rate over a prolonged period of time.

24. An ocular device for the dispensing of an ophthalmic drug according to claim 23 wherein the drug is a member selected from the group consisting of pilocarpine and its pharmaceutically acceptable salts.

25. An ocular device for the dispensing of an ophthalmic drug according to claim 23 wherein the ophthalmic drug is a member selected from the group consisting of epinephrine, ephedrine, norepinephrine, penicillin, tetracycline, oxytetracycline and chlorotetracycline.

26. An oral, osmotic device for the controlled and continuous dispensing of a unit dosage amount of drug to the gastrointestinal tract, said device comprising:

a. a shaped wall formed of a semipermeable material that is permeable to the passage of an external gastrointestinal fluid and is substantially impermeable to drug, said wall having an opening and surrounding;

b. a compartment formed of microporous material and containing a unit dosage amount of drug that is soluble in the fluid and exhibits an osmotic pressure gradient across the wall against the fluid when the device is in the environment of use;

c. a passageway for dispensing the drug, said passageway consisting of at least one micropore that communicates with the opening in the wall and the exterior of the device; and

d. wherein in operation with the device in the environment of use, external fluid is imbibed through the wall into the compartment in a tendency towards osmotic equilibrium at a rate controlled by the permeability of the wall and the osmotic pressure gradient across the wall producing a solution that is dispensed through the passageway from the device at a controlled and continuous rate over a prolonged period of time.

27. The oral device according to claim 26 wherein the drug is mixed with a member selected from the group consisting of inorganic and organic osmotically effective compounds that exhibit an osmotic pressure gradient across the wall against the fluid.

28. The oral device according to claim 26 wherein the drug is a member selected from the group consisting of acetazolamide, potassium chloride, ascorbic acid, acetylsalicyclic acid, levo-dopa, methazolamide, scopolamine, ferrous fumurate, ferrous lactate and nitroglycerin.

29. The oral device according to claim 26 wherein the wall is formed of a member selected from the group consisting of cellulose acetate, cellulose triacetate and cellulose acetate butyrate.

30. The oral device according to claim 26 wherein the microporous material maintains its integrity in the environment of use and has an osmotic reflection coefficient of from 0 to 0.5.

31. The oral device according to claim 30 wherein the reflection coefficient is the hydrostatic pressure difference times the osmotic volume flux divided by the osmotic pressure difference times the hydrostatic volume flux.

32. The oral device according to claim 26 wherein the compartment contains a member selected from the group consisting of a dispersant, emulsifier and wetting agent.

33. The oral device according to claim 26 wherein the wall is formed of an erodible material.

34. The oral device according to claim 26 wherein the compartment is formed of an erodible microporous material.

35. A method for continuously administering an active agent at a controlled rate to the gastrointestinal tract of a warm blooded animal comprising:

A. admitting into the gastrointestinal tract an osmotic device shaped and sized for oral administration with the device comprising;

1. a wall formed of a pharmaceutically acceptable semipermeable material that is permeable to the passage of gastrointestinal fluid and substantially impermeable to the passage of an active agent, said wall having an opening and surrounding;

2. a compartment formed of a microporous material and containing a unit dosage amount of active agent that is soluble in the fluid and exhibits an osmotic pressure gradient across the wall against the fluid;

3. a passageway for dispensing the active agent, said passageway consisting of at least one micropore that communicates with the opening in the wall and the exterior of the device;

B. dissolving said agent in the compartment in gastrointestinal fluid being imbibed through the wall into the compartment at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall to continuously dissolve the agent; and

C. releasing the agent from the device at a therapeutically effective controlled and continuous rate through the passageway to the gastrointestinal tract over a prolonged period of time.

36. A method according to claim 35 wherein the agent is a drug that produces a local or systemic effect on release from the device.

37. A method according to claim 35 wherein the agent is a powder and is mixed with an osmotically effective compound that exhibits an osmotic pressure gradient across the semipermeable wall against the fluid.

38. A method according to claim 35 wherein the microporous material is a solid.