ABUSE RESISTANT OPIOID DRUG-ION EXCHANGE RESIN COMPLEXES HAVING HYBRID COATINGS

• US 20120135077A1
• Filed: 05/28/2008
• Published: 05/31/2012
• Est. Priority Date: 05/31/2007
• Status: Active Grant

• Current Assignee: Tris Pharma Incorporated
• Original Assignee: Tris Pharma Incorporated
• Inventors: Mehta, Ketan, Tu, Yu-Hsing, Chaudhuri, Alivia, Perumal, Ashok
• Granted Patent: US 8,202,542 B1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 47/52 the modifying agent being an inorganic compound, e.g. an inorganic ion that is complexed with the active ingredient
• CPC Class Codes: A61K 47/585 Ion exchange resins, e.g. polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61K 9/2081 with microcapsules or coated microparticles according to A61K9/50
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

A sustained release formulation for opioid drugs is described. The formulation contains an opioid-ion exchange resin complex having a hybrid coating. The hybrid coating contains a cured polyvinylacetate polymer and a pH-dependent enteric coating layer mixed therein. Also provided are methods of making and using same.

Claims

1-25. -25. (canceled)

26. A solid dose formulation having modified release characteristics comprising at least one hybrid coated opioid—

ion exchange resin complex comprising;

a pharmaceutically effective amount of an opioid bound to a pharmaceutically acceptable ion exchange resin; and

a cured hybrid modified release coating layer over the opioid—

ion exchange resin complex, said hybrid coating comprising;

a pH-independent water-permeable, high tensile strength, water insoluble, barrier coating forming component comprising about 70% to about 90% w/w polyvinylacetate (PVA) and about 3 to about 10% w/w of a plasticizer; and

an enteric coating forming component having pH-dependent solubility in an aqueous system which is non-reactive with barrier coating component, said enteric coating component comprising polyvinylacetate phthalate,

wherein said barrier coating forming component and said enteric coating forming component are present in a weight ratio of about 20;

1 to about 3;

1;

and pharmaceutically acceptable excipients.

27. The solid dose formulation according to claim 26, wherein the opioid drug is selected from the group consisting of morphine, oxycodone, hydrocodone, or a salt thereof.

28. The solid dose formulation according to claim 26, wherein the opioid is morphine or morphine sulfate.

30. The solid dose formulation according to claim 26, wherein the solid formulation is a tablet.

31. The solid dose formulation according to claim 26, wherein the solid formulation is granules in a capsule.

33. The solid dose modified release morphine formulation according to claim 31, wherein the barrier forming component further comprises polyvinyl pyrrolidone and sodium laurel sulfate.

34. The solid dose modified release morphine formulation according to claim 31, wherein the enteric coating component further comprises a liquid plasticizer, a solid plasticizer, and at least one or more of a detackifier, a lubricant, an alkalizing agent, a viscosity modifier, and an anti-caking agent.

35. The solid dose modified morphine formulation according to claim 33, wherein the enteric coating component further comprises citroflex triethylcitrate, talc, sodium bicarbonate, polyethylene glycol 3350, stearic acid, sodium alginate, and silica.

36. The solid dose modified release morphine formulation according to claim 31, wherein the cured hybrid coating comprises in about of 20:

1 by weight to about 6;

1 by weight barrier coating component to enteric coating component.

37. The solid dose modified release morphine formulation according to claim 31, wherein the hybrid coating comprises about 30% by weight of the uncoated complex.

38. The solid dose modified release morphine formulation according to claim 31, further comprising a solvating agent.

39. The solid dose modified release morphine formulation according to claim 31, wherein said solid dose is a tablet.

40. The solid dose modified release morphine formulation according to claim 31, further comprising a non-functional coating on the cured hybrid coating layer.

41. The solid dose modified release morphine formulation according to claim 39, wherein the non-functional coating comprises about 2% by weight of the tablet.

42. The solid dose modified release morphine formulation according to claim 31, wherein the tablet comprises a morphine-cation exchange resin complex, at least one filler, at least one lubricant, and at least one diluent.

43. The solid dose modified release morphine formulation according to claim 41, wherein the filler comprises about 1 to 70% by weight of the tablet.

44. The solid dose modified release morphine formulation according to claim 42, wherein the filler is selected from the group consisting of calcium silicate, microcrystalline cellulose, lactose and combinations thereof.

45. The solid dose modified release morphine formulation according to claim 41, wherein the lubricant comprises about 0.01% to about 5% w/w of the tablet.

46. The solid dose modified release morphine formulation according to claim 44, wherein the lubricant is selected from the group consisting of amorphous silica, talc, magnesium stearate, or combinations thereof.

47. The solid dose modified release morphine formulation according to claim 41, further comprising a disintegrant comprising about 1 to about 20% w/w of the tablet.

48. The solid dose modified morphine formulation according to claim 44, wherein the disintegrant is crospovidone.

50. The solid dose formulation according to claim 26, wherein the barrier coating component and enteric polymer component are present in a ratio of about 6:

1 to 4;

1 wt/wt.

51. The solid dose formulation according to claim 26, wherein the plasticizer in the barrier coating component is selected from the group consisting of dibutyl sebacate, propylene glycol, polyethylene glycol, polyvinyl alcohol, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, tributyl citrate, triacetin, Soluphor P, and mixtures thereof.

52. The solid dose formulation according to claim 51, wherein the plasticizer is triacetin.

53. The solid dose formulation according to claim 26, wherein the hybrid coating comprises 25% to 50% by weight of the complex.

54. The solid dose formulation according to claim 53, wherein the hybrid coating comprises 30% to 45% by weight of the complex.

55. The solid dose formulation according to claim 26, wherein the enteric coating component comprises polyvinylacetate phthalate and 10% titanium dioxide

56. The solid dose formulation according to claim 26, wherein the enteric coating component comprises a polvinylacetate phthalate, at least one plasticizer, and one or more selected from the group consisting of a detackifier, a lubricant, an alkalizing agent, a viscosity modifier, and an anti-caking agent.

57. The solid dose formulation according to claim 56, wherein the at least one plasticizer in the enteric coating component comprises a liquid plasticizer and a solid plasticizer.

58. The solid dose formulation according to claim 57, wherein the liquid plasticizer is triethylcitrate.

59. The solid dose formulation according to claim 57, wherein the solid plasticizer is polyethylene glycol 3350.

60. The solid dose formulation according to claim 26, wherein the resin further comprises a release retardant which forms a matrix with the resin complex, wherein said hybrid coating is over said opioid—

ion exchange resin complex—

matrix.

62. The solid dose formulation according to claim 26, wherein said opioid drug—

ion exchange resin complex is in a matrix which further comprises a solvating agent and wherein said hybrid coating is over said opioid—

ion exchange resin complex matrix.

63. The solid dose formulation according to claim 62, wherein said hybrid coating is present in an amount which provides a 40% weight gain over the opioid—

drug ion exchange resin complex—

matrix.

64. The solid dose formulation according to claim 62, wherein the solvating agent is polyvinyl pyrrolidone.

65. The solid dose formulation according to claim 26, wherein the barrier coating component comprises PVA, a stabilizer, a surfactant and a plasticizer.

66. The solid dose formulation according to claim 65, wherein the stabilizer is a polyvinylpyrrolidone.

67. The solid dose formulation according to claim 64, wherein the polyvinyl pyrrolidone comprises about 5 to about 10% w/w of the barrier coating component.

68. The solid dose formulation according to claim 65, wherein the surfactant is sodium lauryl sulfate.

69. The solid dose formulation according to claim 26, wherein the opioid drug is selected from the group consisting of opioid analgesics drugs selected from the group consisting of hydrocodone, morphine, hydromorphone, oxycodone, codeine, levorphanol, meperidine, methadone, oxymorphone, buprenorphine, fentanyl, dipipanone, tramadol, etorphine, dihydroetorphine, butorphanol, levorphanol, or salts thereof or mixtures thereof.

70. The solid dose formulation according to claim 26, wherein the opioid is selected from morphine or morphine sulfate.

29. (canceled)

32. A solid dose modified release morphine formulation comprising:

a pharmaceutically effective amount of morphine bound to a pharmaceutically acceptable cationic exchange resin complex;

a cured hybrid modified release coating layer over the resin complex, said hybrid coating comprising a single layer comprising a barrier forming component comprising polvinylacetate (PVA) and a plasticizer and an enteric coating component comprising PVA-phthalate and at least one plasticizer.

49. (canceled)

61. The solid dose formulation according to claim 61 wherein the release retardant is selected from the group consisting of a polyvinyl acetate polymer, ethyl cellulose, cellulose acetate, acrylic based polymers or copolymers, cellulose phthalate, and mixtures thereof.