SUBLINGUAL AND BUCCAL FILM COMPOSITIONS

• US 20110033542A1
• Filed: 08/07/2009
• Published: 02/10/2011
• Est. Priority Date: 08/07/2009
• Status: Abandoned Application

• Current Assignee: Monosol Rx LLC (Kuraray Company Limited)
• Original Assignee: Monosol Rx LLC (Kuraray Company Limited)
• Inventors: Myers, Garry L., Sanghvi, Pradeep, Boone, Bill J., Bogue, B. Arlie, Hilbert, Samuel D., Hariharan, Madhusudan
• Application Number:
  US12/537,580
• Publication Number:
  US 20110033542A1
• Time in Patent Office: Days
• US Class Current: 424/484
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• 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

Abstract

The present invention relates to products and methods for treatment of various symptoms in a patient, including treatment of pain suffered by a patient. The invention more particularly relates to self-supporting dosage forms which provide an active agent while providing sufficient buccal adhesion of the dosage form. Further, the present invention provides a dosage form which is useful in reducing the likelihood of diversion abuse of the active agent.

Claims

1. A self-supporting film dosage composition comprising:

a. A polymeric carrier matrix;

b. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof; and

c. a buffer sufficient to maximize the absorption of the agonist.

2. The composition of claim 1, wherein said agonist is a partial agonist.

3. The composition of claim 1, wherein said agonist is an opioid agonist.

4. The composition of claim 1, wherein said composition has a local pH of about 4 to about 9.

5. The composition of claim 1, further comprising a therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof.

6. The composition of claim 5, wherein said composition comprises a first and a second region, said first region comprising said agonist and said second region comprising said antagonist.

7. The composition of claim 6, wherein said first region has a local pH of about 4 to about 9.

8. The composition of claim 7, wherein said local pH is about 5.5.

9. The composition of claim 6, wherein said second region has a local pH of about 2 to about 4.

10. The composition of claim 9, wherein said local pH is about 2.

11. The composition of claim 1, wherein said polymeric carrier matrix comprises at least one polymer in an amount of at least 25% by weight of said composition.

12. The composition of claim 1, wherein said buffer is present in an amount of from about 2:

1 to about 1;

5 buffer to agonist.

13. The composition of claim 1, wherein said composition comprises at least one self-supporting film-forming polymer.

14. The film dosage composition of claim 1, wherein said agonist is present in an amount of from about 2 mg to about 16 mg per dosage.

15. The film dosage composition of claim 1, wherein said buffer comprises sodium citrate, citric acid, and combinations thereof.

16. The film dosage composition of claim 1, wherein said buffer comprises acetic acid, sodium acetate, and combinations thereof.

17. A self-supporting film dosage composition comprising:

a. A polymeric carrier matrix;

b. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof;

c. A therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof; and

d. A buffering system;

wherein said buffering system comprises a buffer capacity sufficient to inhibit the absorption of said antagonist during the time which said composition is in the oral cavity of a user.

18. The composition of claim 17, wherein said agonist is a partial agonist.

19. The composition of claim 17, wherein said agonist is an opioid agonist.

20. The composition of claim 17, wherein said composition comprises a first region and a second region, said first region comprising said agonist and said second region comprising said antagonist.

21. The composition of claim 17, wherein said agonist has a local pH of about 4 to about 9.

22. The composition of claim 17, wherein said antagonist has a local pH of about 2 to about 4.

23. A method of treatment, comprising the steps of:

a. Providing a film dosage composition comprising;

i. A polymeric carrier matrix;

ii. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof, and

iii. A buffer in an amount sufficient to maximize the absorption of said agonist; and

b. Administering said film dosage composition to a patient.

24. The method of claim 23, wherein said agonist is a partial agonist.

25. The method of claim 23, wherein said agonist is an opioid agonist.

26. The method of claim 23, wherein said agonist has a local pH of about 4 to about 9.

27. The method of claim 23, wherein said composition further comprises a therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof.

28. The method of claim 27, wherein said antagonist has a local pH of about 2 to about 4.

29. The method of claim 23, wherein said film dosage composition is administered to the user through a mucosal membrane of said patient.

30. The method of claim 29, wherein said film dosage composition remains in the mucosal membrane of said patient for a period of at least 1 minute.

31. A method of treatment, comprising the steps of:

a. Providing a film dosage composition comprising;

i. A polymeric carrier matrix;

ii. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof,

iii. A therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof,

iv. A first buffer in an amount sufficient to obtain a local pH of said agonist of about 4 to about 9;

v. A second buffer in an amount sufficient to obtain a local pH of said antagonist of about 2 to about 4; and

b. Administering said film dosage composition to a user.

32. The method of claim 31, wherein said composition comprises a first and a second region, wherein said first region comprises said agonist and said second region comprises said antagonist.

33. The method of claim 31, wherein said agonist is a partial agonist.

34. The method of claim 31, wherein said agonist is an opioid agonist.

35. A self-supporting film dosage composition comprising:

a. A first region comprising;

i. A first polymeric matrix;

ii. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof, and

iii. A first buffering system in an amount sufficient to optimize the absorption of said agonist;

b. A second region comprising;

i. A second polymeric matrix;

ii. A therapeutically effective amount of an antagonist; and

iii. A second buffering system in an amount sufficient to inhibit the absorption of said antagonist.

36. The composition of claim 35, wherein said agonist is a partial agonist.

37. The composition of claim 35, wherein said agonist is an opioid agonist.

38. The composition of claim 35, wherein said first buffering system is present in an amount sufficient to provide a local pH of said first region of from about 4 to about 9.

39. The composition of claim 35, wherein said first buffering system is present in an amount sufficient to provide a local pH of said first region of about 5.5.

40. The composition of claim 35, wherein said second buffering system is present in an amount sufficient to provide a local pH of said second region of from about 2 to about 4.

41. The composition of claim 35, wherein said second region is coated onto at least one surface of said first region.

42. The composition of claim 35, wherein said second region is laminated to at least one surface of said first region.

43. An orally dissolving film formulation comprising a first region comprising a therapeutically effective amount of an agonist and second region comprising a therapeutically effective amount of an antagonist, wherein said formulation provides an in vivo plasma profile having a Cmax of about 0.624-5.638 ng/ml for said agonist and an in vivo plasma profile having a Cmax of about 46.04-323.75 pg/ml for said antagonist.

44. The formulation of claim 43, wherein said agonist is a partial agonist.

45. The formulation of claim 43, wherein said agonist is an opioid agonist.

46. The formulation of claim 43, wherein said formulation provides a mean AUC of about 5.431-56.238 hr*ng/ml for said agonist.

47. The formulation of claim 43, wherein said formulation provides a mean AUC of about 102.88-812.00 hr*pg/ml for said antagonist.

48. The formulation of claim 43, wherein said formulation comprises about 2 to about 16 mg of said agonist.

49. The formulation of claim 43, wherein said formulation comprises about 0.5 to about 4 mg of said antagonist.

50. A self-supporting film dosage composition comprising:

a. A polymeric carrier matrix;

b. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof;

c. A therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof; and

d. A buffering system sufficient to obtain a local pH of said antagonist of about 2 to about 4.

51. A self-supporting film dosage composition comprising:

a. A polymeric carrier matrix;

b. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof;

c. A therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof; and

d. A buffering system sufficient to inhibit absorption of said antagonist and optimize absorption of said agonist when said film dosage composition is placed in the mouth of a user.

52. A self-supporting film dosage composition comprising:

a. A first region comprising;

i. A first polymeric matrix;

ii. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof, and

iii. A first buffering system in an amount sufficient to optimize absorption of said agonist when said film dosage composition is placed in the mouth of a user; and

b. A second region comprising;

i. A second polymeric matrix;

ii. A therapeutically effective amount of an antagonist; and

iii. A second buffering system in an amount sufficient to inhibit absorption of said antagonist when said film dosage composition is placed in the mouth of a user.

53. The composition of claim 52, wherein said first and second buffering systems are the same.

54. A process of forming a film dosage composition comprising the steps of:

a. Casting a film-forming composition, said film-forming composition comprising;

i. A polymeric carrier matrix;

ii. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof,

iii. A therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof, and

iv. A buffer in an amount sufficient to optimize absorption of said agonist and sufficient to inhibit absorption of said antagonist when said film dosage composition is placed in the mouth of a user; and

b. Drying said film-forming composition to form a self-supporting film dosage composition.

55. A method of treatment, comprising the steps of:

a. Providing a film dosage composition comprising;

i. A polymeric carrier matrix;

ii. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof;

iii. A therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof, and

iv. A buffering system in an amount sufficient to provide an in vivo plasma profile having a Cmax of about 0.624-5.638 ng/ml for said agonist and an in vivo plasma profile having a Cmax of about 41.04-323.75 pg/ml for said antagonist; and

b. Administering said film dosage composition to a user.

56. A self-supporting film dosage composition comprising:

a. A first region comprising;

i. A first polymeric matrix;

ii. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof; and

iii. A first buffering system in an amount sufficient to optimize the absorption of said agonist;

b. A second region comprising;

i. A second polymeric matrix;

ii. A therapeutically effective amount of an antagonist; and

iii. A second buffering system in an amount sufficient to inhibit the absorption of said antagonist

wherein said second region dissolves at a faster rate when placed in the oral cavity of the user than said first region.

57. The composition of claim 56, wherein said first polymeric matrix comprises a moderate-dissolving polymer.

58. The composition of claim 56, wherein said second polymeric matrix comprises a fast-dissolving polymer.

59. The composition of claim 56, wherein said first buffering system is sufficient to provide a local pH for said agonist of from about 4 to about 9.

60. The composition of claim 56, wherein said second buffering system is sufficient to provide a local pH for said antagonist of from about 2 to about 4.

61. A process of forming a film dosage composition comprising the steps of:

a. Casting a first film-forming composition, said first film-forming composition comprising;

i. A polymeric carrier matrix;

ii. A therapeutically effective amount of an agonist or a pharmaceutically acceptable salt thereof, and

iii. A buffer in an amount sufficient to optimize absorption of said agonist when said film dosage composition is placed in the mouth of a user;

b. Casting a second film-forming composition, said second film-forming composition comprising;

i. A polymeric carrier matrix;

ii. A therapeutically effective amount of an antagonist or a pharmaceutically acceptable salt thereof, and

iii. A buffer in an amount sufficient to inhibit absorption of said antagonist when said film dosage composition is placed in the mouth of a user; and

c. Laminating said first film-forming composition and said second film-forming composition together to form a self-supporting film dosage composition.

62. The process of claim 61, wherein said first film-forming composition is dried prior to said step of laminating said first film-forming composition and said second film-forming composition together.

63. The process of claim 61, wherein said second film-forming composition is dried prior to said step of laminating said first film-forming composition and said second film-forming composition together.

64. The process of claim 61, wherein said first film-forming composition is at least partially dried prior to said step of laminating said first film-forming composition and said second film-forming composition together.

65. The process of claim 61, wherein said second film-forming composition is at least partially dried prior to said step of laminating said first film-forming composition and said second film-forming composition together.