Sustained-release gel coated compositions

• US 7,790,215 B2
• Filed: 03/26/2003
• Issued: 09/07/2010
• Est. Priority Date: 03/26/2002
• Status: Active Grant

• Current Assignee: Purdue Pharma L.P.
• Original Assignee: Purdue Pharma L.P.
• Inventors: Wright, Curtis, Oshlack, Benjamin, Sackler, Richard S.
• Primary Examiner(s): Richter; Johann R
• Assistant Examiner(s): Soroush; Ali
• Application Number:
  US10/401,111
• Publication Number:
  US 20030190362A1
• Time in Patent Office: 2,722 Days
• Field of Search: 424/464, 427/2.21, 427/221
• US Class Current: 427/2.21
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2873 Proteins, e.g. gelatin
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

Disclosed in certain embodiments is a coating comprising a pharmaceutically acceptable mixture of gelatin and hydrophobic polymer.

Claims

1. An oral pharmaceutical dosage form comprising an active agent and a sustained-release coating disposed about the active agent, wherein the sustained-release coating comprises a pharmaceutically acceptable mixture of gelatin and hydrophobic polymer, and the hydrophobic polymer is present in an amount of at least 20% based on the total weight of the coating, wherein said dosage form provides sustained release of said active agent over at least 8 hours.

4. The dosage form of claim 1, wherein said hydrophobic polymer comprises a cellulosic polymer.

5. The dosage form of claim 4, wherein said cellulosic polymer is selected from the group consisting of cellulosesters, cellulose diesters, cellulose triesters, cellulose ethers, cellulose ester-ether, cellulose acylate, cellulose diacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose acetate propionate, cellulose acetate butyrate and mixtures thereof.

6. The dosage form of claim 4, wherein said cellulosic polymer comprises ethycellulose.

8. The dosage form of claim 1, wherein said hydrophobic polymer is present in an amount from 20 to about 80% based on the total weight of the sustained-release coating.

11. The dosage form of claim 1, further comprising a plasticizer.

12. The dosage form of claim 11, wherein said plasticizer is selected from the group consisting of hygroscopic plasticizers, non-hygroscopic plasticizers, diethyl phthalate, triethyl citrate, citric acid, mineral oil, lanolin alcohol, petroleum and lanolin alcohols and any mixtures thereof.

13. The dosage form of claim 12, wherein said hygroscopic plasticizer is selected from the group consisting of glycerin, sorbitol, and alkylene glycols.

14. The dosage form of claim 12, wherein said non-hygroscopic plasticizer is selected from the group consisting of maltitol, lactitol, xylitol, hydrogenated starch hydrosylate and partially dehydrogenated glucose syrups.

15. The dosage form of claim 11, wherein said plasticizer is present in an amount from about 5 to about 35% based on the total weight of the sustained-release coating.

16. The dosage form of claim 11, wherein said plasticizer and said gelatin are present in said sustained-release coating in a ratio from about 1:

3 to 1;

15.

17. The dosage form of claim 11, wherein said plasticizer and said gelatin are present in said sustained-release coating in a ratio of about 1:

5.

18. The dosage form of claim 1, wherein said gelatin is present in an amount from about 0.1% to about 60%, based on the total weight of the sustained-release coating.

19. The dosage form of claim 18, wherein said gelatin is present in an amount from about 1% to 20%, based on the total weight of the sustained-release coating.

20. The dosage form of claim 18, wherein said gelatin is present in an amount from about 30 to 60%, based on the weight of the sustained-release coating.

21. The dosage form of claim 1, in the form of a tablet, a capsule, a caplet, spheroids, drug coated beads, microspheres, multiparticulate matrices, or ion-exchange resin beads.

22. The dosage form of claim 1, further comprising a matrix comprising said active agent dispersed therein.

23. The dosage form of claim 1, further comprising a plurality of matrices comprising said active agent dispersed therein.

24. The dosage form of claim 1, wherein said dosage form provides sustained release of said active agent over at least 18 hours.

25. The dosage form of claim 1, wherein said sustained-release coating has a thickness from about 5 to 50 mils.

26. The dosage form of claim 25, wherein said sustained-release coating has a thickness from about 10 to 30 mils.

27. The dosage form of claim 26, wherein said sustained-release coating has a thickness from about 15 to 25 mils.

28. The dosage form of claim 1, wherein said sustained-release coating is applied as an aqueous dispersion.

29. The dosage form of claim 1, wherein said active agent comprises an opioid agonist.

30. The dosage form of claim 29 wherein said opioid agonist is selected from the group consisting of morphine, hydromorphone, hydrocodone, oxycodone, codeine, levorphanol, meperidine, methadone, oxymorphone, buprenorphine, fentanyl and derivatives thereof, dipipanone, tramadol, etorphine, dihydroetorphine, butorphanol, levorphanol, pharmaceutically acceptable salts thereof and mixtures thereof.

31. The dosage form of claim 30, wherein the opioid agonist is selected from the group consisting of oxycodone, hydrocodone and pharmaceutically acceptable salts thereof.

32. The dosage form of claim 1, wherein said active agent comprises an opioid antagonist.

33. The dosage form of claim 32, wherein said opioid antagonist is selected from the group consisting of naltrexone, naloxone, nalmephene, cyclazocine, levallorphan, pharmaceutically acceptable salts thereof and mixtures thereof.

34. The dosage form of claim 33, wherein the opioid antagonist comprises naltrexone or a pharmaceutically acceptable salt thereof.

36. The dosage form of claim 21, wherein said active agent is an opioid antagonist.

37. The dosage form of claim 36, wherein said opioid antagonist is selected from the group consisting of naltrexone, naloxone, nalmephene, cyclazocine, levallorphan, pharmaceutically acceptable salts thereof and mixtures thereof.

38. A dosage form of claim 1, wherein the active agent is in the form of a liquid or semi-solid composition.

39. A dosage form of claim 1, wherein the active agent is in the form of a solid composition.

77. The dosage form of any one of claims 1-3, 40-47, 50-52, or 66-67, wherein said sustained-release coating is a gel coating.

2. An oral pharmaceutical dosage form comprising an active agent and a sustained-release coating disposed about the active agent, wherein the sustained-release coating comprises a pharmaceutically acceptable mixture of gelatin and acrylic polymer.

7. The dosage form of claim 2, wherein said acrylic polymer is selected from the group consisting of acrylic acid and methacrylic acid copolymers, methacrylic acid copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cyanoethyl methacrylate, methyl methacrylate, copolymers, methacrylic acid copolymers, methyl methacrylate copolymers, methyl methacrylate copolymers, methyl methacrylate copolymers, methacrylic acid copolymer, aminoalkyl methacrylate copolymer, methacrylic acid copolymers, methyl methacrylate copolymers, poly(acrylic acid), poly(methacrylic acid, methacrylic acid alkylamide copolymer, poly(methyl methacrylate), poly(methacrylic acid) (anhydride), methyl methacrylate, polymethacrylate, methyl methacrylate copolymer, poly(methyl methacrylate), poly(methyl methacrylate) copolymer, polyacrylamide, aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), glycidyl methacrylate copolymers and mixtures of any of the foregoing.

9. The dosage form of claim 2, wherein said acrylic polymer is present in an amount from about 20 to about 80% based on the total weight of the sustained-release coating.

10. The dosage form of claim 9, wherein said acrylic polymer is present in an amount from about 40 to about 60% based on the total weight of the sustained-release coating.

3. An oral pharmaceutical dosage form comprising a plurality of inert beads, a first layer comprising an active agent disposed about the inert beads, and a second layer comprising a sustained-release coating comprising a pharmaceutically acceptable mixture of gelatin and hydrophobic polymer disposed about the first layer.

35. The dosage form of claim 3 wherein the mean outer diameter of the second layers is about 0.1 mm to about 3 mm.

40. An oral pharmaceutical dosage form comprising an inert core, a first layer and a second layer, the first layer being between the core and the second layer, the first layer comprising naltrexone hydrochloride and the second layer comprising a sustained release coating comprising a mixture of gelatin and hydrophobic polymer.

41. An oral pharmaceutical dosage form comprising an inert core, a first layer, a second layer and a third layer, the first layer being between the core and the second layer, the second layer being between the first layer and the third layer, the first layer comprising naltrexone hydrochloride, the second layer comprising hydrophobic polymer and the third layer comprising a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

42. An oral pharmaceutical dosage form comprising about 10 mg oxycodone hydrochloride, less than about 5.0 mg naltrexone hydrochloride and a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

43. An oral pharmaceutical dosage form comprising a first component comprising about 10 mg oxycodone hydrochloride, and a second component comprising less than about 5.0 mg naltrexone hydrochloride and a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

48. The dosage form of claim 43, wherein the second component comprising an inert core, a first layer and a second layer, the first layer being between the core and the second layer, the first layer comprising said naltrexone hydrochloride and the second layer comprising said sustained-release coating.

49. The dosage form of claim 43, wherein the second component comprises an inert core, a first layer, a second layer and a third layer, the first layer being between the core and the second layer, the second layer being between the first layer and the third layer, the first layer comprising naltrexone hydrochloride, the second layer comprising a hydrophobic polymer and the third layer comprising said sustained-release coating.

44. An oral pharmaceutical dosage form comprising about 20 mg oxycodone hydrochloride, less than about 5.0 mg naltrexone hydrochloride and a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

45. An oral pharmaceutical dosage form comprising a first component comprising about 20 mg oxycodone hydrochloride, and a second component comprising less than about 5.0 mg naltrexone hydrochloride and a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

46. An oral pharmaceutical dosage form comprising about 40 mg oxycodone hydrochloride, less than about 5.0 mg naltrexone hydrochloride and a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

47. An oral pharmaceutical dosage form comprising a first component comprising about 40 mg oxycodone hydrochloride, and a second component comprising less than about 5.0 mg naltrexone hydrochloride and a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

50. An oral pharmaceutical dosage form comprising about 5-20 mg hydrocodone bitartrate, less than about 5.0 mg naltrexone hydrochloride and a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

51. An oral pharmaceutical dosage form comprising a first component comprising about 5-20 mg hydrocodone bitartrate, and a second component comprising less than about 5.0 mg naltrexone hydrochloride and a sustained-release coating comprising a mixture of gelatin and hydrophobic polymer.

52. An oral pharmaceutical dosage form comprising a sustained release substrate comprising a matrix comprising an opioid agonist;

and a sustained-release coating comprising a mixture of gelatin and a hydrophobic polymer disposed about said substrate.

53. The dosage form of claim 52, wherein said matrix is a sustained release matrix and further comprises a hydrophobic material.

54. The dosage form of claim 52, wherein said matrix is an immediate release matrix and said substrate further comprises a sustained release coating disposed about said matrix.

55. The dosage form of claim 53, wherein said substrate further comprises a sustained-release coating disposed about said sustained-release matrix.

56. The dosage form of claim 52, further comprising a protective coating disposed between said substrate and said sustained-release coating.

57. The dosage form of claim 54, further comprising a protective coating disposed between said matrix and said sustained release coating.

58. The dosage form of claim 54, further comprising a protective coating disposed between said sustained release coating and said gelatin coating.

59. The dosage form of claim 52, wherein said substrate provides a sustained release of said opioid agonist for at least 8 hours.

60. The dosage form of claim 52, wherein said substrate provides a sustained release of said opioid agonist for at least 18 hours.

61. The dosage form of claim 52, wherein said sustained-release coating has a thickness from about 5 to 100 mils.

62. The dosage form of claim 52, wherein said sustained-release coating has a thickness from about 60 to 100 mils.

63. The dosage form of claim 52, wherein said sustained-release coating has a thickness from about 15 to 40 mils.

64. The dosage form of claim 52, wherein said opioid agonist is selected from the group consisting of morphine, hydromorphone, hydrocodone, oxycodone, codeine, levorphanol, meperidine, methadone, oxymorphone, buprenorphine, fentanyl and derivatives thereof, dipipanone, tramadol, etorphine, dihydroetorphine, butorphanol, levorphanol, pharmaceutically acceptable salts thereof and mixtures thereof.

65. The dosage form of claim 52, wherein said opioid agonist is selected from the group consisting of oxycodone, pharmaceutically acceptable salts thereof and mixtures thereof.

66. An oral pharmaceutical dosage form comprising a plurality of inert beads, a first layer comprising an active agent selected from the group consisting of an opioid agonist, an opioid antagonist and a mixture thereof, said active agent disposed about the inert beads, a second layer comprising a hydrophobic polymer disposed about the first layer, and a third layer comprising a sustained-release coating comprising gelatin disposed about the second layer.

68. The dosage form of claim 66, wherein said hydrophobic polymer comprises a cellulosic polymer.

69. The dosage form of claim 68, wherein said cellulosic polymer is selected from the group consisting of cellulosesters, cellulose diesters, cellulose triesters, cellulose ethers, cellulose ester-ether, cellulose acylate, cellulose diacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose acetate propionate, cellulose acetate butyrate and mixtures thereof.

70. The dosage form of claim 68, wherein said cellulosic polymer comprises ethycellulose.

71. The dosage form of claim 66, wherein said hydrophobic polymer comprises an acrylic polymer.

72. The dosage form of claim 71, wherein said acrylic polymer is selected from the group consisting of acrylic acid and methacrylic acid copolymers, methacrylic acid copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cyanoethyl methacrylate, methyl methacrylate, copolymers, methacrylic acid copolymers, methyl methacrylate copolymers, methyl methacrylate copolymers, methyl methacrylate copolymers, methacrylic acid copolymer, aminoalkyl methacrylate copolymer, methacrylic acid copolymers, methyl methacrylate copolymers, poly(acrylic acid), poly(methacrylic acid, methacrylic acid alkylamide copolymer, poly(methyl methacrylate), poly(methacrylic acid) (anhydride), methyl methacrylate, polymethacrylate, methyl methacrylate copolymer, poly(methyl methacrylate), poly(methyl methacrylate) copolymer, polyacrylamide, aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), glycidyl methacrylate copolymers and mixtures of any of the foregoing.

73. The dosage form of claim 66, wherein said active agent is an opioid agonist.

74. The dosage form of claim 66, wherein said active agent is an opioid antagonist.

75. The dosage form of claim 73, which provides a sustained release of the opioid agonist for at least 8 hours.

76. The dosage form of claim 73, which provides a sustained release of the opioid agonist for at least 18 hours.

67. An oral pharmaceutical dosage form comprising a plurality of matrices comprising an active agent selected from the group consisting of an opioid agonist, an opioid antagonist and a mixture thereof, said active agent at least partially interdispersed in a hydrophobic polymer;

and a layer comprising a sustained-release coating comprising a mixture of gelatin and a hydrophobic polymer disposed about said matrices.