Multi-layered osmotic device

• US RE39,069 E1
• Filed: 12/03/2001
• Issued: 04/18/2006
• Est. Priority Date: 05/30/1997
• Status: Expired due to Term

• Current Assignee: Osmotica Kereskedelmi Es Szolgaltato Kft (Osmotica Pharmaceuticals Plc)
• Original Assignee: Osmotica Corp.
• Inventors: Faour, Joaquina, Mayorga, Jorge E.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): CHANNAVAJJALA, LAKSHMI SARADA
• Application Number:
  US10/004,772
• Time in Patent Office: 1,597 Days
• Field of Search: 424/473, 424/468, 424/472, 424/474, 424/476, 424/479, 424/482
• US Class Current: 424/473
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

The present invention provides a simple and improved multi-layered osmotic device (1) that is capable of delivering a first active agent in an outer lamina (2) to one environment of use and a second active agent in the core (5) to another environment of use. Particular embodiments of the invention provide osmotic devices in which the first and second active agents are similar or dissimilar. An erodible polymer coat (3) between an internal semipermeable membrane (4) and a second active agent-containing external coat (2) comprises poly(vinylpyrrolidone)-(vinyl acetate) copolymer. This particular erodible polymer results in an improved multi-layered osmotic device possessing advantages over related devices known in the art. The active agent in the core (5) is delivered through a pore (6) containing an erodible plug (7). The osmotic device (1) can be coated by a final finish coat (8).

Claims

1. An improved A multi-layered osmotic device for the controlled delivery of one or more active agents to one or more environments of use wherein the osmotic device comprises:

a) a compressed core comprising a first active agent and an osmotic agent for controlled and continuous release of the drug first active agent;

b) a semipermeable membrane surrounding the core and having a preformed passageway therein, said semipermeable membrane being permeable to a fluid in the environment of use and substantially impermeable to the first active agent;

c) an inert, completely erodible or water soluble polymer coat comprising poly(vinylpyrrolidone)-(vinyl acetate) copolymer partially or substantially completely surrounding the semipermeable membrane and plugging the passageway in the wall semipermeable membrane; and

d) an external coat comprising a second active agent for immediate release of the drug second active agent, wherein the first active agent is released from the core after the polymer coat has partially or completely dissolved or eroded, and the first and second active agents are released into the same or different environments of use to provide a controlled delivery of the one or more active agents.

2. An osmotic device according to claim 1 wherein the compressed core further comprises poly(vinylpyrrolidone).

3. An osmotic device according to claim 1 wherein the semipermeable membrane consists essentially of cellulose acetate and poly(ethylene glycol).

4. An osmotic device according to claim 1 wherein the external coat comprises poly(vinylpyrrolidone) and poly (ethylene glycol).

5. An osmotic device according to claim 1 wherein the second active agent in the external coat comprises a therapeutic agent.

6. An osmotic device according to claim 1 wherein the first active agent in the core comprises a therapeutic agent.

7. An osmotic device according to claim 1 wherein the second active agent in the external coat comprises a therapeutic agent and the first active agent in the core comprises a therapeutic agent.

8. An osmotic device according to claim 7 wherein the first and second active agents are the same.

9. An osmotic device according to claim 8 wherein the first and second active agents are theophylline.

10. An osmotic device according to claim 1 wherein the second active agent in the external coat comprises a therapeutic agent and the first active agent in the core comprises a different therapeutic agent.

11. An osmotic device according to claim 10 wherein the first active agent is pseudoephedrine and the second active agent is loratadine.

12. An osmotic device according to claim 10 wherein the first active agent is ranitidine and the second active agent is a combination of ranitidine and cisapride.

13. An osmotic device according to claim 10 wherein the first active agent is pseudoephedrine and the second active agent is astemizole.

14. An osmotic device according to claim 10 wherein the first active agent is diltiazem and the second active agent is enalapril.

15. An osmotic device according to claim 1, wherein the one or more environments of use comprises a first environment of use and a different second environment of use.

16. An osmotic device according to claim 15, wherein the first environment of use is the gastric region and the second environment of use is farther down the gastrointestinal tract of a mammal.

17. An osmotic device according to claim 1, wherein the first and second active agents are released into the same environment of use.

18. An osmotic device according to claim 1, wherein the controlled delivery of one or more active agents includes one or more of pH-dependent, pH-independent, diffusion controlled, dissolution controlled, pseudo-zero order, zero-order, pseudo-first order, first-order, second-order, rapid, slow, delayed, timed, and sustained delivery.

19. An osmotic device according to claim 1, wherein at least a portion of the polymer coat dissolves or erodes in fluid present in an environment of use after the external coat has at least partially dissolved in an environment of use.

20. An osmotic device according to claim 1, wherein the polymer coat is one or more of soluble in the same environment of use in which the external coat is soluble, and soluble in the same environment of use in which the core is soluble.

21. An osmotic device according to claim 1, wherein the semipermeable membrane comprises a plasticizer and one or more of a cellulose ether, cellulose ester and cellulose-ester-ether.

22. An osmotic device according to claim 1, wherein the external coat further comprises poly(vinylpyrrolidone).

23. An osmotic device according to claim 1, wherein the polymer coat further comprises one or more of talc and poly(ethylene glycol).

34. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first and second active agents are independently selected at each occurrence from the group consisting of antibacterial, antihistamine, decongestant, anti-inflammatory, antiparasitic, antiviral, local anesthetic, antifungal, amoebicidal, trichomonocidal, analgesic, antiarthritic, antiasthmatic, anticoagulant, anticonvulsant, antidepressant, antidiabetic, antineoplastic, antipsychotic, neuroleptic, antihypertensive, muscle relaxant, depressant, hypnotic, sedative, psychic energizer, tranquilizer, antiparkinson, muscle contractant, anti-microbial, antimalarial, hormonal, contraceptive, sympathomimetic, diuretic, hypoglycemic, ophthalmic, electrolyte, diagnostic and cardiovascular agent.

35. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first and second active agents are independently selected at each occurrence from the group consisting of pesticide, herbicide, insecticide, antioxidant, plant growth instigator, sterilization agent, catalyst, chemical reagent, food product, nutrient, cosmetic, vitamin, sterility inhibitor, fertility instigator, microorganism, flavoring agent, sweetener, and cleansing agent.

39. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the inert, completely erodible or water soluble polymer coat comprises at least two different polymers.

40. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the delivery of the first active agent is delayed with respect to delivery of the second active agent.

41. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first active agent is ranitidine and the second active agent is a combination of ranitidine and cisapride.

42. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first active agent is pseudoephedrine and the second active agent is astemizole.

43. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first active agent is pseudoephedrine and the second active agent is loratadine.

44. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first active agent is diltiazem and the second active agent is enalapril.

45. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first and second active agents are theophylline.

46. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first active agent is a decongestant and the second active agent is an antihistamine.

47. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first active agent is a first antihypertensive agent and the second active agent is a different second antihypertensive agent.

48. The multi-layered osmotic device of claim 1, 24, 25, 26 or 27, wherein the first active agent is a gastric acid inhibitor and the second active agent is a gastrointestinal emptying adjunct agent.

24. A multi-layered osmotic device for the controlled delivery of one or more active agents to one or more environments of use wherein the osmotic device comprises:

a) a compressed core comprising a first active agent and an osmotic agent for controlled and continuous release of the first active agent;

b) a semipermeable membrane surrounding the core and having a preformed passageway therein, said semipermeable membrane being permeable to a fluid in the environment of use and substantially impermeable to the first active agent;

c) an inert, completely erodible or water soluble polymer coat partially or completely surrounding the semipermeable membrane and plugging the passageway in the semipermeable membrane; and

d) an external coat applied to and covering the inert polymer coat and comprising a second active agent for immediate release of the second active agent, wherein the first active agent is released from the core after the polymer coat has partially or completely dissolved or eroded, and the first and second active agents are released into the same or different environments of use to provide a controlled delivery of the one or more active agents.

28. The multi-layered osmotic device of claim 24, 25, 26 or 27, wherein the first and second active agents each comprise a therapeutic agent.

29. The multi-layered osmotic device of claim 24, 25, 26 or 27, wherein the first and second active agents are the same.

30. The multi-layered osmotic device of claim 24, 25, 26 or 27, wherein the first and second active agents are different.

31. The multi-layered osmotic device of claim 24, 25, 26 or 27, wherein the first and second active agents are released into different environments of use.

32. The multi-layered osmotic device of claim 24, 25, 26 or 27, wherein the first and second active agents are released into the same environment of use.

33. The multi-layered osmotic device of claim 24, 25, 26 or 27, wherein the controlled delivery of one or more active agents includes one or more of pH-dependent, pH-independent, diffusion controlled, dissolution controlled, pseudo-zero order, zero-order, pseudo-first order, first-order, second-order, rapid, slow, delayed, timed, and sustained delivery.

25. A multi-layered osmotic device for the controlled delivery of one or more active agents to one or more environments of use wherein the osmotic device comprises:

a) a compressed core comprising a first active agent and at least one osmotic agent for controlled and continuous release of the first active agent;

b) a semipermeable membrane surrounding the core and having at least one preformed passageway therein;

c) an inert, completely erodible or water soluble polymer coat partially or completely surrounding the semipermeable membrane and plugging the passageway in the semipermeable membrane; and

d) an external coat applied to and covering the inert polymer coat and comprising a second active agent for immediate release of the second active agent, wherein the first active agent is released from the core after the polymer coat has partially or completely dissolved or eroded, and the first and second active agents are released into the same or different environments of use.

26. A multi-layered osmotic device for the controlled delivery of one or more active agents to one or more environments of use wherein the osmotic device comprises:

a) a compressed core comprising a first active agent and at least one osmotic agent for controlled and continuous release of the first active agent;

b) a semipermeable membrane surrounding the core and having at least one preformed passageway therein;

c) an inert, completely erodible or water soluble polymer coat partially or completely surrounding the semipermeable membrane and plugging the at least one preformed passageway in the semipermeable membrane; and

d) an external coat applied to and covering the inert polymer coat and comprising a second active agent for release of the second active agent, wherein the first active agent is released from the core after the polymer coat has partially or completely dissolved or eroded, and the first and second active agents are released into the same or different environments of use.

27. A multi-layered osmotic device for the controlled delivery of one or more active agents to one or more environments of use wherein the osmotic device comprises:

a) a compressed core comprising a first active agent and at least one osmotic agent for controlled and continuous release of the first active agent;

b) a semipermeable membrane surrounding the core and having at least one preformed passageway therein;

c) an inert, completely erodible or water soluble polymer coat partially or completely surrounding the semipermeable membrane and plugging the at least one preformed passageway in the semipermeable membrane; and

d) an external coat applied to and covering the inert polymer coat and comprising a second active agent for immediate, rapid, delayed, slow, sustained, pseudo-first order, pseudo-zero order, timed, controlled or combination thereof release of the second active agent, wherein the first active agent is released from the core after the polymer coat has partially or completely dissolved or eroded, and the first and second active agents are released into the same or different environments of use.

36. A multi-layered osmotic device for the controlled delivery of one or more active agents to one or more environments of use wherein the osmotic device comprises:

a) a compressed core comprising a first active agent and at least one osmotic agent for controlled and continuous release of the first active agent;

b) a semipermeable membrane surrounding the core and having at least one preformed passageway therein;

c) an inert, completely erodible or water soluble polymer coat partially or completely surrounding the semipermeable membrane and plugging the passageway in the semipermeable membrane and comprising poly(vinylpyrrolidone)-(vinyl acetate) copolymer and a second polymer; and

d) an external coat applied to and covering the inert polymer coat and comprising a second active agent for immediate release of the second active agent, wherein the first active agent is released from the core after the polymer coat has partially or completely dissolved or eroded, and the first and second active agents are released into the same or different environments of use.

37. The multi-layered osmotic device of claim 36, wherein the semipermeable membrane comprises a plasticizer and one or more of a cellulose ether, cellulose ester and cellulose-ester-ether.

38. The multi-layered osmotic device of claim 37, wherein the polymer coat further comprises one or more of talc and poly(ethylene glycol).

49. A multi-layered osmotic device for the controlled delivery of one or more active agents to one or more environments of use wherein the osmotic device comprises:

a) a compressed core comprising a first active agent and at least one osmotic agent for controlled and continuous release of the first active agent;

b) a semipermeable membrane surrounding the core and having at least one preformed passageway therein;

c) an inert, completely erodible or water soluble polymer coat partially or completely surrounding the semipermeable membrane and plugging the at least one preformed passageway in the semipermeable membrane, wherein the inert, completely erodible or water soluble polymer coat comprises poly(vinylpyrrolidone)-(vinyl acetate) copolymer; and

d) an external coat applied to and covering the inert polymer coat and comprising a second active agent for release of the second active agent, wherein the first active agent is released from the core after the polymer coat has partially or completely dissolved or eroded, and the first and second active agents are released into the same or different environments of use.

50. The multi-layered osmotic device of claim 49, wherein the inert, completely erodible or water soluble polymer coat further comprises a second polymer.

51. The multi-layered osmotic device of claim 49, wherein the semipermeable membrane comprises a plasticizer and one or more of a cellulose ether, cellulose ester and cellulose-ester-ether.

52. A multi-layered osmotic device for the controlled delivery of one or more active agents to one or more environments of use wherein the osmotic device comprises:

a) a compressed core comprising a first active agent and at least one osmotic agent for controlled and continuous release of the first active agent;

b) a semipermeable membrane surrounding the core and having at least one preformed passageway therein;

c) an inert, completely erodible or water soluble polymer coat partially or completely surrounding the semipermeable membrane and plugging the at least one preformed passageway in the semipermeable membrane and comprising poly(vinylpyrrolidone)-(vinyl acetate) copolymer; and

d) an external coat applied to and covering the inert polymer coat and comprising a second active agent for immediate, rapid, delayed, slow, sustained, pseudo-first order, pseudo-zero order, timed, controlled or combination thereof release of the second active agent, wherein the first active agent is released from the core after the polymer coat has partially or completely dissolved or eroded, and the first and second active agents are released into the same or different environments of use.

53. The multi-layered osmotic device of claim 52, wherein the inert, completely erodible or water soluble polymer coat further comprises a second polymer.

54. The multi-layered osmotic device of claim 52, wherein the semipermeable membrane comprises a plasticizer and one or more of a cellulose ether, cellulose ester and cellulose-ester-ether.