OPTIMIZED NIACIN COMPOSITIONS IN PHARMACEUTICAL PRODUCTS

• US 20120039957A1
• Filed: 08/12/2011
• Published: 02/16/2012
• Est. Priority Date: 08/13/2010
• Status: Abandoned Application

• Current Assignee: Acura Pharmaceuticals Incorporated (Abuse Deterrent Pharma LLC)
• Original Assignee: Acura Pharmaceuticals Incorporated (Abuse Deterrent Pharma LLC)
• Inventors: BRZECZKO, Albert W., GILKAY, John
• Application Number:
  US13/208,956
• Publication Number:
  US 20120039957A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/455 Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 39/00 General protective or antinoxious agents
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y10T 428/2982 Particulate matter [e.g., sphere, flake, etc.]

Abstract

The present invention includes compositions and methods related to forms of niacin with enhanced in-vivo absorption and bioavailability. Such enhanced delivery of niacin in the presence of food may be achieved by size reduction of crystalline niacin, use of amorphous forms of niacin, and/or pH modulation in the presence on organic acids.

Claims

1. A pharmaceutical composition comprising a stable nanoparticle comprising niacin, wherein the nanoparticle has a particle size of about 100 nm to about 300 nm.

2. The pharmaceutical composition of claim 1, wherein nanoparticle further comprises surface stabilizing ingredients.

3. The pharmaceutical composition of claim 2, wherein the surface stabilizing ingredients comprise one or more of a surfactant, a powder flow aid, or a polymer.

4. The pharmaceutical composition of claim 2, wherein the surface stabilizing ingredient comprises sodium lauryl sulfate.

5. The pharmaceutical composition of claim 1, wherein the niacin is amorphous.

6. The pharmaceutical composition of claim 1, further comprising an organic acid.

7. The pharmaceutical composition of claim 6, wherein the niacin and organic acid are mixed at a particulate level.

8. The pharmaceutical composition of claim 6, wherein the niacin and organic acid form cocrystals.

9. The pharmaceutical composition of claim 6, wherein at least a portion of the niacin and organic acid forms a molecular dispersion.

10. The pharmaceutical composition of claim 6, wherein the organic acid has a pKa of about 2.0 to about 6.5.

11. The pharmaceutical composition of claim 6, wherein the organic acid comprises at least one of oxalic acid, glycine, taurine, citric acid, pyruvic acid, alanine, maleic acid, glutaric acid, or tartaric acid.

12. The pharmaceutical composition of claim 6, wherein the ratio of niacin to organic acid is from about 1:

5 to about 5;

1.

13. The pharmaceutical composition of claim 6, wherein the ratio of niacin to organic acid is from about 1:

3 to about 3;

1.

14. A pharmaceutical composition comprising amorphous niacin, wherein the amorphous niacin comprises a solid dispersion of niacin and a polymer.

15. The pharmaceutical composition of claim 14, wherein the polymer comprises amino methacrylate copolymer.

16. The pharmaceutical composition of claim 14, wherein the polymer comprises poloxamer.

17. The pharmaceutical composition of claim 14, wherein the polymer is present in an amount of up to about 1000% w/w of niacin.

18. The pharmaceutical composition of claim 14, wherein the polymer is present in an amount of about 20% w/w to about 400% w/w of niacin.

19. The pharmaceutical composition of claim 14, wherein the niacin comprises a stable nanoparticle.

20. The pharmaceutical composition of claim 14, further comprising an organic acid.

21. The pharmaceutical composition of claim 20, wherein the niacin and organic acid are mixed at a particulate level.

22. The pharmaceutical composition of claim 20, wherein the niacin and organic acid form cocrystals.

23. The pharmaceutical composition of claim 20, wherein at least a portion of the niacin and organic acid forms a molecular dispersion.

24. The pharmaceutical composition of claim 20, wherein the organic acid has a pKa of about 2.0 to about 6.5.

25. The pharmaceutical composition of claim 20, wherein the organic acid comprises at least one of oxalic acid, glycine, taurine, citric acid, pyruvic acid, alanine, maleic acid, glutaric acid, or tartaric acid.

26. The pharmaceutical composition of claim 20, wherein the ratio of niacin to organic acid is from about 1:

5 to about 5;

1.

27. The pharmaceutical composition of claim 20, wherein the ratio of niacin to organic acid is from about 1:

3 to about 3;

1.

28. The pharmaceutical composition of claim 14, wherein the polymer comprises a low molecular weight polymer.

29. The pharmaceutical composition of claim 14, wherein the polymer comprises a water soluble polymer.

30. The pharmaceutical composition of claim 14, wherein the polymer comprises a polymer soluble in low pH media.

31. A pharmaceutical composition comprising,

(a) an opioid analgesic;

(b) niacin in an amount sufficient to cause flushing if greater than a prescribed amount of the analgesic of the pharmaceutical composition is ingested;

wherein the niacin comprises a stable nanoparticle.

32. The composition of claim 31, wherein the nanoparticle further comprises surface stabilizing agents.

33. The composition of claim 31, wherein the niacin is amorphous.

34. The composition of claim 31, further comprising an organic acid.

35. The composition of claim 34, wherein the niacin and organic acid are cocrystals.

36. The composition of claim 31, wherein the composition is in unit dose form.

37. The composition of claim 31, wherein the composition is in a caplet, capsule, pill, gel, soft gelatin capsule, or compressed tablet form.

38. The composition of claim 31, wherein the analgesic is present in an amount of about 5 mg to about 200 mg on a solid weight basis.

39. The composition of claim 31, wherein the analgesic comprises hydrocodone or a therapeutically acceptable salt thereof.

40. The composition of claim 31, wherein the analgesic comprises oxycodone or a therapeutically acceptable salt thereof.

41. The composition of claim 31, further comprising a gel forming polymer

42. The composition of claim 31, further comprising a nasal tissue irritant.

43. A pharmaceutical composition comprising

(a) a drug susceptible to abuse;

and

(b) niacin in an amount sufficient to cause flushing if greater than a prescribed amount of the drug of the pharmaceutical composition is ingested;

wherein the niacin comprises a stable nanoparticle.

44. The composition of claim 43, wherein the nanoparticle further comprises surface stabilizing agents.

45. The composition of claim 43, wherein the niacin is amorphous.

46. The composition of claim 43, further comprising an organic acid.

47. The composition of claim 46, wherein the niacin and organic acid are cocrystals.

48. The composition of claim 43, wherein the composition is in unit dose form.

49. The composition of claim 43, wherein the composition is in a caplet, capsule, pill, gel, soft gelatin capsule, or compressed tablet form.

50. The composition of claim 43, further comprising a gel forming polymer

51. The composition of claim 43, further comprising a nasal tissue irritant.

52. A pharmaceutical composition comprising

(a) a drug susceptible to abuse;

and

(b) niacin in a sub-therapeutic amount;

wherein the niacin comprises a stable nanoparticle.

53. The composition of claim 52, wherein the nanoparticle further comprises surface stabilizing agents.

54. The composition of claim 52, wherein the niacin is amorphous.

55. The composition of claim 52, further comprising an organic acid.

56. The composition of claim 55, wherein the niacin and organic acid are cocrystals.

57. The composition of claim 52, wherein the composition is in unit dose form.

58. The composition of claim 52, wherein the composition is in a caplet, capsule, pill, gel, soft gelatin capsule, or compressed tablet form.

59. The composition of claim 52, further comprising a gel forming polymer

60. The composition of claim 52, further comprising a nasal tissue irritant.

61. A pharmaceutical composition comprising

(a) a drug susceptible to abuse;

and

(b) amorphous niacin in an amount sufficient to cause flushing if greater than a prescribed amount of the drug of the pharmaceutical composition is ingested;

wherein the amorphous niacin comprises a solid dispersion of niacin and a polymer.

62. The pharmaceutical composition of claim 61, wherein the polymer comprises amino methacrylate copolymer.

63. The pharmaceutical composition of claim 61, wherein the polymer comprises poloxamer.

64. The pharmaceutical composition of claim 61, wherein the polymer is present in an amount of up to about 1000% w/w of niacin.

65. The pharmaceutical composition of claim 61, wherein the polymer is present in an amount of about 20% w/w to about 400% w/w of niacin.

66. The pharmaceutical composition of claim 61, wherein the niacin comprises a stable nanoparticle.

67. The pharmaceutical composition of claim 61, further comprising an organic acid.

68. The pharmaceutical composition of claim 67, wherein the niacin and organic acid are mixed at a particulate level.

69. The pharmaceutical composition of claim 67, wherein the niacin and organic acid form cocrystals.

70. The pharmaceutical composition of claim 61, wherein the composition is in unit dose form.

71. The pharmaceutical composition of claim 61, wherein the composition is in a caplet, capsule, pill, gel, soft gelatin capsule, or compressed tablet form.

72. The pharmaceutical composition of claim 61, further comprising a gel forming polymer

73. The pharmaceutical composition of claim 61, further comprising a nasal tissue irritant.

74. A pharmaceutical composition comprising

(a) a drug susceptible to abuse;

(b) niacin in an amount sufficient to cause flushing if greater than a prescribed amount of the drug of the pharmaceutical composition is ingested; and

(c) an organic acid.

75. The pharmaceutical composition of claim 74, wherein the niacin and organic acid are coprocessed.

76. The pharmaceutical composition of claim 74, wherein the niacin and organic acid form cocrystals.

77. The pharmaceutical composition of claim 74, wherein at least a portion of the niacin and organic acid forms a molecular dispersion.

78. The pharmaceutical composition of claim 74, wherein the organic acid has a pKa of about 2.0 to about 6.5

79. The pharmaceutical composition of claim 74, wherein the organic acid comprises at least one of oxalic acid, glycine, taurine, citric acid, pyruvic acid, alanine, maleic acid, glutaric acid, or tartaric acid.

80. The pharmaceutical composition of claim 74, wherein the ratio of niacin to organic acid is from about 1:

5 to about 5;

1.

81. The pharmaceutical composition of claim 74, wherein the ratio of niacin to organic acid is from about 1:

3 to about 3;

1.

82. The pharmaceutical composition of claim 74, wherein the niacin is amorphous.

83. The pharmaceutical composition of claim 82, wherein the amorphous niacin comprises a solid dispersion of niacin and a polymer.

84. The pharmaceutical composition of claim 74, wherein the niacin comprises a stable nanoparticle.

85. The pharmaceutical composition of claim 84, wherein the nanoparticle further comprises surface quenching agents.

86. The pharmaceutical composition of claim 74, wherein the composition is in unit dose form.

87. The pharmaceutical composition of claim 74, wherein the composition is in a caplet, capsule, pill, gel, soft gelatin capsule, or compressed tablet form.

88. The pharmaceutical composition of claim 74, further comprising a gel forming polymer.

89. The pharmaceutical composition of claim 74, further comprising a nasal tissue irritant.