MULTIDIRECTIONAL MUCOSAL DELIVERY DEVICES AND METHODS OF USE

• US 20110189259A1
• Filed: 06/23/2009
• Published: 08/04/2011
• Est. Priority Date: 06/23/2008
• Status: Abandoned Application

• Current Assignee: Biodelivery Sciences International Incorporated
• Original Assignee: Biodelivery Sciences International Incorporated
• Inventors: Finn, Andrew, Vasisht, Niraj
• Application Number:
  US12/996,101
• Publication Number:
  US 20110189259A1
• Time in Patent Office: Days
• US Class Current: 424/444
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present invention relates to a pharmaceutical dosage form for transmucosal delivery of an active agent to two or more mucosal surfaces. The dosage form is presented as a transmucosal delivery device. The devices of the invention may include at least two mucoadhesive surfaces. The devices may further include an intermediate layer disposed between the mucoadhesive layers. The pharmaceutical can be incorporated in any one or all of the mucoadhesive layers or the intermediate layer. Upon application, the device adheres to at least two surfaces, providing transmucosal delivery of the drug to at least two surfaces.

Claims

1. A method of transmucosally delivering an active agent to a subject in need thereof, comprising:

administering to a subject in need thereof a thin and flexible pharmaceutical delivery device wherein the pharmaceutical delivery device comprises;

a first mucoadhesive surface for transmucosal delivery of an active agent;

a second mucoadhesive surface, opposing the first mucoadhesive surface, for transmucosal delivery of an active agent; and

an active agent incorporated into the device,

wherein the first and second mucoadhesive surfaces are defined by at least one thin and flexible mucoadhesive film layer; and

wherein an effective amount of the active agent is delivered to the subject.

2. The method of claim 1, wherein the device is bioerodable.

3. The method of claim 1, wherein the first and second mucoadhesive surfaces are defined by a single mucoadhesive layer.

4. The method of claim 1, wherein the first and second mucoadhesive surfaces are defined by at least a first and a second thin and flexible mucoadhesive film layer.

5. The method of claim 4, wherein the device further comprises an intermediate layer disposed between the two mucoadhesive surfaces.

6. The method of claim 5, wherein the intermediate layer comprises an abuse-resistant matrix and an antagonist associated with the abuse-resistant matrix such that the antagonist is substantially transmucosally unavailable.

7. The method of claim 5, wherein the intermediate layer comprises a microencapsulated antagonist.

8. The method of claim 1, wherein the mucoadhesive layer comprises a microencapsulated antagonist.

9. The method of claim 4, wherein the intermediate layer is occlusive to the active agent.

10. The method of claim 4, wherein the active agent is incorporated into the first mucoadhesive layer, and the second mucoadhesive layer.

11. The method of claim 1, wherein the active agent is an abusable drug.

12. The method of anyone of the preceding claims wherein the active agent is an opioid.

13. The method of claim 12, wherein the active agent is buprenorphine.

14. The method of claim 12, wherein the active agent is fentanyl.

15. The method of claim 6, wherein the antagonist is naloxone.

16. The method of claim 1, wherein the active agent is transmucosally delivered to two or more mucosal surfaces.

17. The method of claim 1, wherein the device is administered to a subject by applying the device to a mucosal cavity of the subject such that there is adhesion of the delivery device to at least two surfaces of the mucosal cavity and diffusion of the active agent across the first mucoadhesive surface and the second mucoadhesive surface.

18. The method of claim 17, wherein the effective amount of active agent is delivered to the subject in less than about 1 hour.

19. The method of claim 17, wherein the effective amount of active agent is delivered to the subject in less than about 30 minutes.

20. The method of any one of claim 1 or 6, wherein the subject does not experience significant nausea.

21. The method of claim 14, wherein onset of pain relief is achieved in less than about 15 minutes.

22. The method of claim 14, wherein the T_max is less than about 1.5 hours.

23. The method of claim 14, wherein the T_max is less than about 1 hour.

24. The method of claim 14, wherein the T_max is less than about 0.5 hours.

25. The method of claim 14, wherein the T_max is less than about 0.25 hours.

26. The method of claim 14, wherein the device comprises about 800 μ

g of fentanyl.

27. The method of claim 26, wherein the C_max is greater than about 2 ng/mL.

28. The method of claim 26, wherein the C_max is greater than about 3 ng/mL.

29. The method of claim 26, wherein the C_max is greater than about 4 ng/mL.

30. The method of claim 26, wherein the more than about 30% of the fentanyl becomes bioavailable.

31. The method of claim 26, wherein more than about 60% of the fentanyl becomes bioavailable.

32. The method of claim 26, wherein more than about 70% of the fentanyl becomes bioavailable.

33. The method of claim 13, wherein the device contains between about 0.1 mg to about 60 mg of buprenorphine.

34. The method of claim 33, wherein T_max is less than about 100 minutes.

35. The method of claim 33, wherein T_max is less than about 80 minutes.

36. The method of claim 33, wherein T_max is less than about 60 minutes.

37. The method of claim 33, wherein T_max is less than about 30 minutes.

38. The method of claim 33, wherein T_max is less than about 20 minutes.

39. The method of claim 33, wherein more than 30% of the buprenorphine becomes bioavailable.

40. The method of claim 33, wherein more than 50% of the buprenorphine becomes bioavailable.

41. The method of claim 33, wherein more than 60% of the buprenorphine becomes bioavailable.

42. A method of treating addiction, comprising the method of any of the preceding claims.

43. A method of treating pain, comprising administering an active agent to a subject by any of the methods of any of the preceding claims.

44. The method of claim 43, wherein the pain is breakthrough cancer pain.

45. The method according to any of the preceding claims wherein an effective amount of the active agent is delivered to the subject in one unit dose.