Process of making stable abuse-deterrent oral formulations
View Patent ↗The present disclosure relates to cured pharmaceutical compositions designed to reduce the potential for improper administration of drugs that are subject to abuse, the process of curing such composition in order to improve the dissolution stability, method of using the same for treatment of pain.
1. A pharmaceutical composition comprising solid microparticles or formulated microparticles prepared by:
(a) preparing a mixture at a temperature sufficient to form a melt comprising:
(i) oxycodone, myristic acid, beeswax and carnauba wax, or
(ii) oxycodone in the form of a myristic acid salt, beeswax and carnauba wax;
(b) forming solid microparticles from the melt;
(c) optionally further formulating the solid microparticles with additional pharmaceutically acceptable excipients to provide formulated microparticles, and
(d) curing the solid microparticles or the formulated microparticles at one or more curing temperatures from 26° C. to 38° C., for a minimum of about 48 hours to provide cured solid microparticles or cured formulated microparticles.
2. The pharmaceutical composition of claim 1 wherein the mixture of step (a) further includes stearoyl polyoxyl-32 glycerides.
3. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 26° C. to 36° C.
4. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 26° C. to 34° C.
5. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 26° C. to 32° C.
6. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 26° C. to 30° C.
7. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 26° C. to 28° C.
8. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 27° C. to 36° C.
9. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 28° C. to 38° C.
10. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 28° C. to 36° C.
11. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 28° C. to 35° C.
12. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 28° C. to 34° C.
13. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 28° C. to 33° C.
14. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 28° C. to 32° C.
15. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 28° C. to 30° C.
16. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 30° C. to 38° C.
17. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 30° C. to 36° C.
18. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 30° C. to 34° C.
19. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 30° C. to 32° C.
20. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 32° C. to 38° C.
21. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 32° C. to 36° C.
22. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 32° C. to 34° C.
23. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 34° C. to 38° C.
24. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 34° C. to 36° C.
25. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured at one or more curing temperatures from 36° C. to 38° C.
26. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 26° C.
27. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 27° C.
28. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 28° C.
29. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 29° C.
30. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 30° C.
31. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 31° C.
32. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 32° C.
33. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 33° C.
34. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 34° C.
35. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 35° C.
36. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 36° C.
37. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 37° C.
38. The pharmaceutical composition of claim 1 , wherein the solid microparticles are cured at 38° C.
39. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 3 days.
40. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 4 days.
41. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 5 days.
42. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 6 days.
43. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 7 days.
44. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 8 days.
45. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 9 days.
46. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 10 days.
47. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 11 days.
48. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 12 days.
49. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 13 days.
50. The pharmaceutical composition of claim 1 , wherein the solid microparticles or the formulated microparticles are cured for about 14 days.
51. The pharmaceutical composition of claim 1 , comprising myristic acid in about 30 wt. % to about 70 wt. % of the pharmaceutical composition.
52. The pharmaceutical composition of claim 1 , comprising myristic acid in about 40 wt. % to about 60 wt. % of the pharmaceutical composition.
53. The pharmaceutical composition of claim 1 , wherein the combination of beeswax and carnauba wax comprises about 20 wt. % to about 60 wt. % of the pharmaceutical composition.
54. The pharmaceutical composition of claim 1 , wherein the combination of beeswax and carnauba wax comprises about 30 wt. % to about 50 wt. % of the pharmaceutical composition.
55. The pharmaceutical composition of claim 1 , comprising:
a. about 9 mg to about 72 mg oxycodone or an equivalent amount of a myristic acid salt thereof;
b. about 30 wt. % to about 70 wt. % of myristic acid; and
c. about 20 wt. % to about 60 wt. % of a combination of beeswax and carnauba wax.
56. The pharmaceutical composition of claim 1 , comprising:
a. about 9 mg to about 72 mg oxycodone or an equivalent amount of a myristic acid salt thereof;
b. about 40 wt. % to about 60 wt. % of myristic acid; and
c. about 30 wt. % to about 50 wt. % of a combination of beeswax and carnauba wax.
57. The pharmaceutical composition of claim 1 , comprising:
a. about 9 mg to about 36 mg oxycodone or an equivalent amount of a myristic acid salt thereof;
b. about 40 wt. % to about 60 wt. % of myristic acid; and
c. about 30 wt. % to about 50 wt. % of a combination of beeswax and carnauba wax.
58. A capsule comprising the pharmaceutical composition of claim 1 .
59. A capsule comprising the pharmaceutical composition of claim 55 .
60. A capsule comprising the pharmaceutical composition of claim 56 .
61. A capsule comprising the pharmaceutical composition of claim 57 .
62. A method of treating pain comprising administering the pharmaceutically composition of claim 1 to a patient in need thereof.
63. A method of treating pain comprising administering the pharmaceutical composition of claim 55 to a patient in need thereof.
64. A method of treating pain comprising administering the pharmaceutical composition of claim 57 to a patient in need thereof.
65. A method of treating pain comprising administering the capsule of claim 58 to a patient in need thereof.
66. A method of treating pain comprising administering the capsule of claim 59 to a patient in need thereof.
67. A method of treating pain comprising administering the capsule of claim 61 to a patient in need thereof.