Oral transmucosal delivery of drugs or any other ingredients via the inner buccal cavity

• US 6,210,699 B1
• Filed: 04/01/1999
• Issued: 04/03/2001
• Est. Priority Date: 04/01/1999
• Status: Expired due to Term

• Current Assignee: Allergan Sales LLC (Abbvie Incorporated)
• Original Assignee: Watson Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Baker, Joseph L., Acharya, Ramesh N.
• Primary Examiner(s): Azpuru, Carlos A.
• Application Number:
  US09/285,018
• Time in Patent Office: 733 Days
• Field of Search: 424/435, 514/772.3
• US Class Current: 424/435
• CPC Class Codes: A61K 9/006 Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
• CPC Class Codes: A61K 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28

Abstract

A device and method for the oral transmucosal delivery of active substances to the oral cavity utilizing an unplasticized polyvinyl pyrrolidone polymer (PVP) as the primary mucoadhesive. The device is applied and adheres to the mucosa of the oral cavity without causing side effects or leaving an unpleasant taste. Preferably the device is a bilayer tablet having a mucoadhesive layer and an overlying active substance containing layer. The mucoadhesive layer may contain PVP as the only adhesive or may be combined with other hydrophilic polymeric substances. The active layer also contains a hydrophilic polymer carrier. The layers in the device dissolve and release the active substance to the oral cavity and is particularly adapted for the delivery of substances active in the oral cavity such as breath fresheners and substances to combat dry mouth. It is also useful for the delivery of ionic drugs such as peptides.

Claims

1. A device for the oral transmucosal delivery of active substances to the oral cavity comprising a mucoadhesive layer and at least one overlying active substance layer said mucoadhesive layer having one surface adapted to contact the mucosal surface of the oral cavity for adhering thereto and an opposing surface in contact with and adhering to an overlying active substance containing layer characterized in that the mucoadhesive layer contains a mucoadhesive composition comprising at least 50% by weight of a non-plasticized polyvinyl pyrrolidone polymer having a weight average molecular weight of between about 10,000 and 700,000.

2. A device according to claim 1 wherein said mucoadhesive layer contains from 20 to 99% by weight of said mucoadhesive composition.

3. A device according to claim 2 wherein said mucoadhesive composition consists of non-plasticized polyvinyl pyrrolidone polymer.

4. A device according to claim 2 wherein said mucoadhesive composition comprises about 50 to 95% by weight of non-plasticized polyvinyl pyrrolidone polymer and 5 to 50% by weight of an additional functionally suitable hydrophilic polymer or copolymer.

5. A device according to claim 4 wherein said additional hydrophilic polymer or copolymer is a member selected from the group consisting of acrylic acid polymers, hydroxypropyl cellulose, methylcellulose, polyethylene oxide, polyvinyl pyrrolidone, gaur-gum, pectins, starches, gelatin and casein.

6. A device according to claim 3 or 4 wherein the overlying active substance layer contains from about 3 to 60% by weight of a hydrophilic polymer in which the active substance is intimately contained.

7. A device according to claim 6 wherein the active substance is a breath freshener and is present in the active substance layer in amounts of between about 10 to 60% by weight.

8. A device according to claim 7 wherein the mucoadhesive layer also contains an active substance in amounts of between about 5 to 40% by weight.

9. A device according to claim 8 wherein the mucoadhesive composition content of the mucoadhesive layer is present in amounts of between about 20 to 60% by weight.

10. A device according to claim 9 wherein the breath freshener is an odorant member selected from the group consisting of peppermint, spearmint, menthol, grape, cherry, lemon, strawberry, orange, licorice, lime and any mixtures thereof.

11. A device according to claim 8 wherein the surface area of said mucoadhesive layer adapted for contact with the mucosal surface is between about 0.5 and 10 cm².

12. A device according to claim 11 wherein said device is a tablet.

13. A device according to claim 12 wherein the thickness of the mucoadhesive layer is between about 0.1 and 3 mm.

14. A device according to claim 6 wherein the active substance is a drug and is present in the active substance layer in amounts of between about 0.1 to 10% by weight.

15. A device according to claim 14 wherein the drug is an ionic drug.

16. A device according to claim 15 wherein said ionic drug is a peptide.

17. A device according to claim 14 wherein the mucoadhesive layer also contains a chemical permeation enhancer in amounts of between about 2 to 20% by weight.

18. A device according to claim 17 wherein the chemical permeation enhancer is a bile acid or a salt thereof.

19. A device according to claim 18 wherein said drug is an ionic drug.

20. A device according to claim 19 wherein said ionic drug is a peptide.

21. A device according to claim 14 wherein the surface area of said mucoadhesive layer adapted for contact with the mucosal surface is between about 0.5 and 10 cm².

22. A device according to claim 21 wherein said device is a tablet.

23. A device according to claim 22 wherein the thickness of the mucoadhesive layer is between about 0.1 and 3 mm.

24. A method for the oral transmucosal delivery of active substances to the oral cavity comprising the steps of:

a) applying to the mucosa of said oral cavity a device comprising a mucoadhesive layer and at least one overlying active substance layer said mucoadhesive layer having one surface which is in contact with the mucosal surface of the oral cavity and adhering thereto and having an opposing surface in contact with and adhering to an overlying active substance containing layer characterized in that the mucoadhesive layer contains a mucoadhesive composition comprising at least 50% by weight of a non-plasticized polyvinyl pyrrolidone polymer having a weight average molecular weight of between about 10,000 and 700,000; and

b) retaining said device adhering to said mucosa until said active substance has been released in said oral cavity.

25. A method according to claim 24 wherein said mucoadhesive layer contains from 20 to 99% by weight of said mucoadhesive composition.

26. A method according to claim 25 wherein said mucoadhesive composition consists of non-plasticized polyvinyl pyrrolidone polymer.

27. A method according to claim 25 wherein said mucoadhesive composition comprises about 50 to 95% by weight of non-plasticized polyvinyl pyrrolidone polymer and 5 to 50% by weight of an additional functionally suitable hydrophilic polymer or copolymer.

28. A method according to claim 27 wherein said additional hydrophilic polymer or copolymer is a member selected from the group consisting of acrylic acid polymers, hydroxypropyl cellulose, methylcellulose, polyethylene oxide, polyvinyl pyrrolidone, gaur-gum, pectins, starches, gelatin and casein.

29. A method according to claim 26 or 27 wherein the overlying active substance layer contains from about 3 to 60% by weight of a hydrophilic polymer in which the active substance is intimately contained.

30. A method according to claim 29 wherein the active substance is a breath freshener and is present in the active substance layer in amounts of between about 10 to 60% by weight.

31. A method according to claim 30 wherein the mucoadhesive layer also contains an active substance in amounts of between about 5 to 40% by weight.

32. A method according to claim 31 wherein the mucoadhesive composition content of the mucoadhesive layer is present in amounts of between about 20 to 60% by weight.

33. A method according to claim 32 wherein the device is adhered to the hard palate.

34. A method according to claim 33 wherein the breath freshener is an odorant member selected from the group consisting of peppermint, spearmint, menthol, grape, cherry, lemon, strawberry, orange, licorice, lime and any mixtures thereof.

35. A method according to claim 33 wherein the surface area of said mucoadhesive layer adapted for contact with the mucosal surface is between about 0.5 and 10 cm².

36. A method according to claim 35 wherein said device is a tablet.

37. A method according to claim 36 wherein the thickness of the mucoadhesive layer is between about 0.1 and 3 mm.

38. A method according to claim 30 wherein the active substance is a drug and is present in the active substance layer in amounts of between about 0.1 to 10% by weight.

39. A method according to claim 38 wherein the drug is an ionic drug.

40. A method according to claim 39 wherein said ionic drug is a peptide.

41. A method according to claim 38 wherein the mucoadhesive layer also contains a chemical permeation enhancer in amounts of between about 2 to 20% by weight.

42. A method according to claim 41 wherein the chemical permeation enhancer is a bile acid or a salt thereof.

43. A method according to claim 42 wherein said drug is an ionic drug.

44. A method according to claim 43 wherein said ionic drug is a peptide.

45. A method according to claim 38 wherein the surface area of said mucoadhesive layer adapted for contact with the mucosal surface is between about 0.5 and 10 cm².

46. A method according to claim 45 wherein said device is a tablet.

47. A method according to claim 46 wherein the thickness of the mucoadhesive layer is between about 0.1 and 3 mm.