Osmotic device having a preformed passageway that increases in size

• US 6,599,284 B2
• Filed: 11/30/2000
• Issued: 07/29/2003
• Est. Priority Date: 01/21/2000
• Status: Expired due to Term

• Current Assignee: Osmotica Pharmaceutical Corporation (Osmotica Pharmaceuticals Plc)
• Original Assignee: Osmotica Corp.
• Inventors: Faour, Joaquina
• Primary Examiner(s): Bennett, Henry
• Assistant Examiner(s): PATEL, NIHIR B
• Application Number:
  US09/728,859
• Publication Number:
  US 20020099361A1
• Time in Patent Office: 971 Days
• Field of Search: 604/890, 604/892.1, 604/897
• US Class Current: 604/892.1
• 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 osmotic device (1) that is capable of providing a controlled release of active agent contained in the core (4) through a preformed passageway (5) into an environment of use. The preformed passageway (5) increases in size during use of the osmotic device (1) thereby increasing the release rate of the active agent, enabling the release of large particles containing active agent, and enabling the release of active agents that are substantially insoluble in the environment of use.

Claims

1. An osmotic device comprising a core comprising an active agent and at least one excipient, a semipermeable membrane surrounding the core and comprising a preformed passageway that increases in size during use and an optical scored region of the membrane adjacent the passageway, wherein the preformed passageway is larger after use than it is prior to use of the osmotic device, and the internal pressure of the device increases during use causing a membrane edge defining the passageway to rupture.

2. The osmotic device of claim 1, wherein the release rate of active agent increases during use.

3. The osmotic device of claim 1, wherein the amount of active agent released is greater than that amount of active agent released by another osmotic device of approximately similar construction but not having a preformed passageway that increases in size.

4. The osmotic device of claim 1, wherein at least 80% of the active agent is released by the end of use.

5. The osmotic device of claim 1, wherein at least 90% of the active agent is released by the end of use.

6. The osmotic device of claim 1, wherein the preformed passageway increases in size by at least 10%.

7. The osmotic device of claim 1, wherein the preformed passageway increases in size by at least 25%.

8. The osmotic device of claim 1, wherein the preformed passageway increases in size by at least 50%.

9. The osmotic device of claim 1, wherein the preformed passageway increases in size by at least 75%.

10. The osmotic device of claim 1, wherein the preformed passageway increases in size by at least 100%.

11. The osmotic device of claim 1, wherein the preformed passageway is formed by mechanical means during manufacture of the osmotic device.

12. The osmotic device of claim 1, wherein the preformed passageway is plugged with a soluble material that dissolves during use of the osmotic device.

13. The osmotic device of claim 1, wherein the preformed passageway increases in size by dissolution or breakage of the semipermeable membrane.

14. The osmotic device of claim 1, wherein the semipermeable membrane dissolves or tears in a predetermined manner.

15. The osmotic device of claim 1, wherein the shape of the preformed passageway after enlargement approximates a predetermined shape.

16. The osmotic device of claim 1, wherein the core comprises a first layer comprising the active agent and the at least one excipient and a second layer comprising a swellable material or an osmotic agent.

17. The osmotic device of claim 1, wherein the core comprises a nucleus comprising a swellable material or an osmotic agent and a coating surrounding the nucleus and comprising the active substance and the at least one excipient.

18. The osmotic device of claim 1 further comprising one or more coatings on the exterior of the semipermeable membrane.

19. The osmotic device of claim 18, wherein the one or more coatings are independently selected at each occurrence from the group consisting of:

a drug-containing coating, a release rate modifying coating, a porous coating;

a soluble coating, an insoluble coating, a semipermeable membrane; and

a delayed release coating.

20. The osmotic device of claim 1, wherein the extent to which the passageway increases in size is related to the viscosity, molecular weight or degree of substitution of the at least one excipient.

21. The osmotic device of claim 1, wherein an increase in the viscosity, molecular weight or degree of substitution of the at least one excipient is related to an increase in the extent to which the passageway increases in size.

22. The osmotic device of claim 1, wherein the at least one excipient is independently selected at each occurrence from the group consisting of an osmagent, an osmopolymer, a lubricant, a glidant, adsorbent, antioxidant, buffering agent, colorant, flavorant, sweetening agent, tablet antiadherent, tablet binder, tablet and capsule diluent, tablet direct compression excipient, tablet disintegrant, tablet opaquant and tablet polishing agent.

23. An osmotic device comprising:

a core comprising an osmopolymer and an active agent;

a semipermeable membrane surrounding the core;

a preformed passageway in the semipermeable membrane; and

an optional scored region in the membrane adjacent the passageway;

wherein the passageway increases in size during use, the preformed passageway is larger after use than it is prior to use of the osmotic device, the internal pressure of the device increases during use causing a membrane edge defining the passageway to rupture, and the release rate of the active agent increases during use or the amount of active agent released is greater than that amount of active agent released from another osmotic device of approximately similar construction but not having a passageway that increases in size during use.

24. The osmotic device of claim 23, wherein the preformed passageway increases in size in a predetermined manner.

25. The osmotic device of claim 23, wherein the preformed passageway increases in size in a manner in a random manner.

26. The osmotic device of claim 23, wherein the semipermeable membrane dissolves or breaks to effect an increase in the size of or a change in the shape of the preformed passageway.

27. The osmotic device of claim 23, wherein the semipermeable membrane is adapted to dissolve or break in a predetermined manner.

28. The osmotic device of claim 23, wherein the release rate of active agent increases during use.

29. The osmotic device of claim 23, wherein the amount of active agent released is greater than that amount of active agent released by another osmotic device of approximately similar construction but not having a preformed passageway that increases in size.

30. The osmotic device of claim 23, wherein at least 80% of the active agent is released by the end of use.

31. The osmotic device of claim 23, wherein at least 90% of the active agent is released by the end of use.

32. The osmotic device of claim 23, wherein the preformed passageway increases in size by at least 10%.

33. The osmotic device of claim 23, wherein the preformed passageway increases in size by at least 25%.

34. The osmotic device of claim 23, wherein the preformed passageway increases in size by at least 50%.

35. The osmotic device of claim 23, wherein the preformed passageway increases in size by at least 75%.

36. The osmotic device of claim 23, wherein the preformed passageway increases in size by at least 100%.

37. The osmotic device of claim 23, wherein the preformed passageway is formed by mechanical means during manufacture of the osmotic device.

38. The osmotic device of claim 23, wherein the preformed passageway is plugged with a soluble material that dissolves during use of the osmotic device.

39. The osmotic device of claim 23, wherein the preformed passageway increases in size by dissolution or breakage of the semipermeable membrane.

40. The osmotic device of claim 23, wherein the semipermeable membrane dissolves or tears in a predetermined manner.

41. The osmotic device of claim 23, wherein the shape of the preformed passageway after enlargement approximates a predetermined shape.

42. The osmotic device of claim 23, wherein the core comprises a first layer comprising the active agent and the at least one excipient and a second layer comprising a swellable material or an osmotic agent.

43. The osmotic device of claim 23, wherein the core comprises a nucleus comprising a swellable material or an osmotic agent and a coating surrounding the nucleus and comprising the active substance and the at least one excipient.

44. The osmotic device of claim 23, further comprising one or more coatings on the exterior of the semipermeable membrane.

45. The osmotic device of claim 44, wherein the one or more coatings are independently selected at each occurrence from the group consisting of:

a drug-containing coating, a release rate modifying coating, a porous coating;

a soluble coating, an insoluble coating, a semipermeable membrane and a delayed release coating.

46. The osmotic device of claim 23, wherein the extent to which the passageway increases in size is related to the viscosity, molecular weight or degree of substitution of the at least one excipient.

47. The osmotic device of claim 23, wherein an increase in the viscosity, molecular weight or degree of substitution of the at least one excipient is related to an increase in the extent to which the passageway increases in size.

48. The osmotic device of claim 23, wherein the at least one excipient is independently selected at each occurrence from the group consisting of an osmagent, an osmopolymer, a lubricant, a glidant, adsorbent, antioxidant, buffering agent, colorant, flavorant, sweetening agent, tablet antiadherent, tablet binder, tablet diluent, tablet direct compression excipient, tablet disintegrant, tablet opaquant, and tablet polishing agent.

57. The osmotic device of claim 23 comprising:

a core comprising an osmopolymer, an osmagent, an active agent, at least one other pharmaceutical excipient;

a semipermeable membrane surrounding the core and comprising at least one cellulose ester and a plasticizer; and

a preformed passageway in the semipermeable membrane;

wherein the passageway increases in size during use and the release rate of the active agent increases during use or the amount of active agent released is greater than that amount of active agent released from a similar osmotic device not having a passageway that increases in size during use.

58. The osmotic device of claim 57 further comprising:

an inert water soluble coating surrounding the semipermeable membrane and plugging the preformed passageway.

59. The osmotic device of claim 58 further comprising:

an external active agent-containing coating surrounding the inert water soluble coating.

60. The osmotic device of claim 59, wherein the active agent is nifedipine, the osmopolymer is hydroxypropyl methylcellulose, the osmagent is sodium chloride, the at least one cellulose ester is cellulose acetate, and the plasticizer is poly(ethylene oxide).

61. The osmotic device of claim 57, wherein the semipermeable membrane comprises at least one etched portion adjacent the preformed passageway and the preformed passageway increases in size along the etched portion.

49. A method for making an osmotic device having a preformed passageway that increases in size during use comprising the steps of:

forming a core comprising an active agent and at least one excipient;

covering said core with a semipermeable membrane; and

perforating said semipermeable membrane with a laser to form at least one preformed passageway that increases in size during use of the osmotic device and optionally to form at least one scored region in the membrane adjacent the passageway,

whereby the internal pressure of the device increases during use causing a membrane edge defining the passageway to rupture.

50. The method of claim 49, wherein the perforating step comprises the step of:

perforating said semipermeable membrane by firing a laser beam at a predetermined section of said semipermeable membrane for a predetermined period of time, the laser having a predetermined pulse period and a predetermined pulse width sufficient to form a preformed passageway that increases in size during use.

51. The method of claim 49, wherein the formation of said preformed passageway comprises unplugging the preformed passageway by dissolution of a soluble material during use of the osmotic device.

52. The method of claim 49, wherein said increase in size of said passageway is caused by tearing said semipermeable membrane.

53. The method of claim 49 further comprising the step of:

covering the semipermeable membrane and plugging the preformed passageway with another coating.

54. The method of claim 53 wherein the other coating is a water soluble coating.

55. The method of claim 49 further comprising the steps of:

covering the semipermeable membrane and plugging the preformed passageway with an inert first water soluble coating; and

covering the first water soluble coating with an active agent-containing second water soluble coating.

56. The method of claim 55, wherein the step of perforating comprises:

perforating the semipermeable membrane with a laser such that a preformed passageway having at least one adjacent etching is formed.

62. A controlled release device that provides a controlled release of an active agent during use, the device comprising:

a core comprising an active agent and at least one excipient, wherein the core undergoes an increase in internal pressure during use of the device and after exposure of the core to an aqueous medium;

a membrane surrounding the core and comprising at least one preformed passageway that increases in size during use of the device, and optionally comprising a scored region adjacent the at least one preformed passageway;

wherein

the increase in internal pressure of the device causes a membrane edge defining the passageway to rupture and the passageway to increase in size.