Laminated osmotic system for dispensing beneficial agent

• US 4,014,334 A
• Filed: 02/02/1976
• Issued: 03/29/1977
• Est. Priority Date: 02/02/1976
• Status: Expired due to Term

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Ayer, Atul D., Theeuwes, Felix
• Primary Examiner(s): Medbery, Aldrich F.
• Application Number:
  US05/654,194
• Time in Patent Office: 421 Days
• Field of Search: 128/260, 128/261, 128/268, 128/272, 424/15, 424/19, 424/20, 424/21, 424/22, 424/33, 424/37
• US Class Current: 424/427
• 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 system for delivering a beneficial agent to an environment of use is disclosed. The system comprises a laminate surrounding a compartment and has a passageway through the laminate for releasing agent from the compartment. The laminate comprises at least two laminae; one consisting of a semipermeable, polymeric material that is permeable to the passage of an external fluid and maintains its physical and chemical integrity in the environment of use, and one consisting of a semipermeable polymeric material that is permeable to the passage of the fluid, substantially impermeable to the passage of agent and maintains its physical and chemical integrity in the presence of agent. The compartment comprises an active agent that is either soluble in the external fluid and exhibits an osmotic pressure gradient across the laminate against the fluid, or the agent has limited solubility in the fluid and it is mixed with an osmotically effective compound that is soluble in the fluid and exhibits an osmotic pressure gradient across the laminate against the fluid. In operation, agent is released from the system by fluid being imbibed through the laminate into the compartment at a rate controlled by the permeability of the laminate and the osmotic pressure gradient across the laminate producing a solution containing agent, or a solution of compound containing agent which solution in either operation is released through the passageway at a controlled and continuous rate over a prolonged period of time.

Claims

1. An osmotic system for the controlled and continuous dispensing of a beneficial agent to an environment of use, said system comprising:

a. a shaped wall comprising a laminate, said laminate comprising a semipermeable lamina that is permeable to the passage of an external fluid and which lamina substantially maintains its physical and chemical integrity in the environment of use; and

a semipermeable lamina that is permeable to the passage of an external fluid, substantially impermeable to the passage of agent and which lamina substantially maintains its physical and chemical integrity in the presence of fluid and agent, said wall surrounding;

b. a compartment containing the beneficial agent;

c. a passageway in the wall communicating with the compartment and the exterior of the system for dispensing agent from the system; and

d. wherein in operation when the system is in the environment of use, fluid from the environment is continuously imbibed through the wall into the compartment 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 agent that is dispensed through the passageway at a controlled and continuous rate over a prolonged period of time.

2. The osmotic system according to claim 1 wherein the laminae are formed of a member selected from the group consisting of semipermeable homopolymer and copolymer materials.

3. The osmotic system according to claim 1 wherein each lamina consists essentially of a unit lamina forming material with the laminae in laminar relation to form an integral laminated wall.

4. The osmotic system according to claim 1 wherein the lamina that maintains its integrity in the presence of fluid and agent faces the compartment.

5. The osmotic system according to claim 1 wherein the lamina that maintains its integrity in the environment of use is distant from the compartment and is formed of a hydrophilic semipermeable polymer.

6. The osmotic system according to claim 1 wherein the system is sized, shaped and adapted as a dosage form for administering an agent to the gastrointestinal tract.

7. The osmotic system according to claim 1 wherein the passageway is formed in the environment of use.

8. The osmotic system according to claim 1 wherein the agent is a member selected from the group consisting of locally and systemically acting drugs.

9. The osmotic system according to claim 1 wherein the beneficial agent is a member selected from the group consisting of acetazolamide, methazolamide, potassium chloride, ascorbic acid, niacin, meprobamate, salicylamide, theophylline monoethanolamine, aminophylline, procainamide, colchicine and atropine.

10. The osmotic system according to claim 1 wherein the beneficial agent is soluble in the fluid and exhibits an osmotic pressure gradient across the wall against the fluid.

11. The osmotic system according to claim 1 wherein the beneficial agent is mixed with an osmotically effective compound that is soluble in the fluid and exhibits an osmotic pressure gradient across the wall against the fluid.

12. An osmotic system for the controlled and continuous dispensing of a beneficial agent to an environment of use, said system comprising:

a. a shaped laminate that is permeable to the passage of an external fluid and substantially impermeable to the passage of agent, said laminate comprising a pair of laminae, with one lamina consisting of a semipermeable material that is essentially non-erodible and exhibits substantial inertness to compounds and fluids present in the environment of use, and with one lamina consisting of a semipermeable material that is essentially non-erodible and exhibits substantial inertness to fluid and agent;

b. the laminate surrounding and forming a compartment containing the beneficial agent that is soluble in the fluid and exhibits an osmotic pressure gradient across the laminate against the fluid;

c. a passageway in the laminate communicating with the compartment and the exterior of the system for dispensing agent from the system; and

d. wherein in operation when the system is in the environment of use, fluid from the environment is continuously imbibed through the laminate into the compartment in a tendency towards osmotic equilibrium at a rate determined by the permeability of the laminate and the osmotic pressure gradient across the laminate, thereby continuously dissolving agent that is dispensed through the passageway at a controlled and continuous rate over a prolonged period of time.

13. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein each lamina is formed of a different polysaccharide.

14. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein each lamina is formed of a different cellulose ester having a degree of substitution greater than 0 and up to 3 inclusive.

15. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein each lamina is independently selected from the group consisting of cellulose acylates, cellulose diacylates, cellulose triacylates, cellulose acetate, cellulose diacetate and cellulose triacetate.

16. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein the system is sized, shaped and adapted for placement in a vagina.

17. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein the system is sized, shaped and adapted for placement in an eye.

18. The osmmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein the agent is a member selected from the group consisting of idoxuridine, phenylephrine, pilocarpine, pilocarpine salts, eserine, carbachol, phospholine idodine, demecarium bromide, cyclopentolate, homatropine, scopolamine and epinephrine.

19. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein the lamina that maintains its integrity in the environment of use is impermeable to the passage of agent.

20. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein the lamina that maintains its integrity in the environment of use is impermeable to the passage of compounds present in the environment.

21. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein the lamina inert to agent is impermeable to the passage of agent.

22. The osmotic system for the controlled and continuous dispensing of an agent according to claim 12 wherein the lamina inert to agent is impermeable to compounds present in the environment.

23. An osmotic system for the controlled and continuous dispensing of a beneficial agent to an environment of use, said system comprising:

a. a shaped laminate comprising two laminae, with one lamina consisting of a semipermeable material that is permeable to the passage of an external fluid, substantially impermeable to compounds present in the environment of use, and substantially maintains its physical and chemical integrity in the environment of use, and with one lamina consisting of a semipermeable material that is permeable to the passage of an external fluid, substantially impermeable to the passage of agent and compounds present in the environment of use, and substantially maintains its physical and chemical integrity in the presence of fluid and agent;

b. the laminate surrounding and forming a compartment containing the agent;

c. a passageway in the laminate communicating with the compartment and the exterior of the system for dispensing agent from the system; and

d. wherein in operation when the system is in the environment of use, fluid from the environment is continuously imbibed through the laminate into the compartment in a tendency towards osmotic equilibrium at a rate determined by the permeability of the laminate and the osmotic pressure gradient across the laminate, thereby forming a solution containing agent that is dispensed through the passageway at a controlled and continuous rate over a prolonged period of time.

24. The osmotic system according to claim 23 wherein the agent is a drug soluble in the external fluid and exhibits an osmotic pressure gradient across the laminate against the fluid.

25. The osmotic system according to claim 23 wherein the agent has limited solubility in the fluid and is mixed with an osmotically effective compound that exhibits an osmotic pressure gradient across the laminate against the fluid.

26. The osmotic system according to claim 23 wherein the lamina that is substantially impermeable to agent is the interior surface of the laminate positioned adjacent to the compartment and is formed of a unit, semipermeable material selected from the group consisting of cellulose esters and cellulose ethers.

27. The osmotic system according to claim 23 wherein the lamina that maintains its integrity in the environment of use is the exterior surface of the laminate positioned distant from the compartment and is formed of a unit, semipermeable material selected from the group consisting of cellulose esters and cellulose ethers possessing different physical and chemical properties from the material forming the interior surface of the laminate.

28. The osmotic system according to claim 23 wherein the agent is a member selected from the group consisting of tolbutamide, tolazamide, chloropropamide, mannitol, hexanitrate, tranylcypromine, progestational and estrogenic agents.

29. The osmotic system according to claim 23 wherein the compartment contains an osmotically effective compound that exhibits an osmotic pressure of from 0 up to 500 atmospheres.

30. The osmotic system according to claim 23 wherein the passageway is formed before the system is placed in the environment of use.

31. The osmotic system according to claim 23 wherein the lamina that substantially maintains its integrity in the environment of use is substantially impermeable to the passage of agent.

32. The osmotic system according to claim 23 wherein the lamina that substantially maintains its integrity in the environment of use is substantially impermeable to the passage of compounds present in the environment of use to agents and osmotically effective compounds present in the compartment.

33. An osmotic system for the controlled and continuous dispensing of an active agent to an environment of use, said system comprising:

a. a compartment containing an active agent;

b. a shaped laminated wall surrounding and forming the compartment, said wall formed of a plurality of semipermeable laminae comprising a lamina positioned adjacent to the compartment that maintains its physical and chemical integrity in the presence of agent, and a lamina positioned distant from the compartment that faces the environment and maintains its physical and chemical integrity when the system is in the environment;

c. a passageway in the laminated wall communicating with the compartment and the exterior of the system for dispensing agent from the system; and

,

d. wherein in operation when the system is in the environment of use, fluid from the environment is continuously imbibed through the laminated wall into the compartment in a tendency towards osmotic equilibrium at a rate determined by the permeability of the laminated wall and the osmotic pressure gradient across the wall, thereby continuously dissolving agent that is dispensed through the passageway at a controlled and continuous rate over a prolonged period of time.

34. The osmotic system for the controlled and continuous dispensing of an agent according to claim 33 wherein the laminae are formed of a member selected from the group consisting of homopolymeric and copolymeric semipermeable materials.

35. The osmotic system for the controlled and continuous dispensing of an agent according to claim 33 wherein the laminae are permeable to the passage of an external fluid, substantially impermeable to compounds present in the environment of use and substantially impermeable to agents and compounds present in the compartment.

36. The osmotic system for the controlled and continuous dispensing of an active agent according to claim 33 wherein the laminae are formed of a different material selected from the group consisting of hydrophilic and hydrophobic homopolymeric and copolymeric semipermeable materials.