Injectable flowable composition comprising buprenorphine
View Patent ↗The present invention is directed to a buprenorphine sustained release delivery system capable of delivering buprenorphine, a metabolite, or a prodrug thereof for a duration of about 14 days to about 3 months. The buprenorphine sustained release delivery system includes a flowable composition and a solid implant for the sustained release of buprenorphine, a metabolite, or a prodrug thereof. The implant is produced from the flowable composition. The buprenorphine sustained release delivery system provides in situ 1-month and 3-month release profiles characterized by an exceptionally high bioavailability and minimal risk of permanent tissue damage and typically no risk of muscle necrosis.
1. An injectable composition comprising: (i) 8 wt % to 30 wt % of buprenorphine in the form of a free base or a pharmaceutically acceptable salt; (ii) 15 wt % to 70 wt % of a poly(DL-lactide-co-glycolide) copolymer; and (iii) 10 wt % to 70 wt % of N-methyl-2-pyrrolidone; wherein the composition is transformed in situ into an implant by contact with a bodily fluid.
2. The composition of claim 1 , wherein the composition comprises from 3 milligrams to about 300 milligrams of buprenorphine in the form of the free base or the pharmaceutically acceptable salt.
3. The composition of claim 1 , wherein the copolymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer.
4. The composition of claim 1 , wherein the poly(DL-lactide-co-glycolide) copolymer has an average molecular weight from 5,000 Daltons to 40,000 Daltons.
5. An injectable composition consisting of: (i) 8 wt % to 30 wt % of buprenorphine in the form of a free base or a pharmaceutically acceptable salt; (ii) 15 wt % to 70 wt % of a poly(DL-lactide-co-glycolide) copolymer; and (iii) 10 wt % to 70 wt % of N-methyl-2-pyrrolidone; wherein the composition is transformed in situ into an implant by contact with a bodily fluid.
6. The composition of claim 5 , wherein the poly(DL-lactide-co-glycolide) copolymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer.
7. The composition of claim 5 , wherein the poly(DL-lactide-co-glycolide) copolymer has an average molecular weight from 5,000 Daltons to 40,000 Daltons.
8. The composition of claim 5 , wherein the composition comprises from 3 milligrams to about 300 milligrams of buprenorphine in the form of a free base or pharmaceutically acceptable salt.
9. The composition of claim 5 , wherein the poly(DL-lactide-co-glycolide) copolymer is a 50/50, 55/45, 60/40, 65/35, 70/30, 75/25, 80/20, 85/15, 90/10, or 95/5 poly(DL-lactide-co-glycolide) copolymer.
10. An injectable composition comprising: (i) 8 wt % to 30 wt % of buprenorphine in the form of a free base or a pharmaceutically acceptable salt; (ii) 15 wt % to 70 wt % of a poly(DL-lactide-co-glycolide) copolymer; and (iii) 10 wt % to 70 wt % of N-methyl-2-pyrrolidone.
11. A method for treating opioid dependency in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the composition of claim 1 to treat the opioid dependency.
12. A method for treating opioid dependency in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the composition of claim 5 to treat the opioid dependency.
13. A method for treating opioid dependency in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the composition of claim 10 to treat the opioid dependency.
14. An injectable composition consisting of: (i) 8 wt % to 30 wt % of buprenorphine in the form of a free base or a pharmaceutically acceptable salt; (ii) 15 wt % to 70 wt % of a poly(DL-lactide-co-glycolide) copolymer; and (iii) 10 wt % to 70 wt % of N-methyl-2-pyrrolidone.
15. A method for treating opioid dependency in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the composition of claim 14 to treat the opioid dependency.
16. The composition of claim 1 , wherein the buprenorphine is in the form of the free base.
17. The composition of claim 5 , wherein the buprenorphine is in the form of the free base.
18. The composition of claim 17 , wherein the composition comprises from 3 milligrams to about 300 milligrams of the buprenorphine.
19. The composition of claim 10 , wherein the buprenorphine is in the form of the free base.
20. The composition of claim 10 , wherein the poly(DL-lactide-co-glycolide) copolymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer.
21. The composition of claim 14 , wherein the buprenorphine is in the form of the free base.
22. The composition of claim 21 , wherein the composition comprises from 3 milligrams to about 300 milligrams of the buprenorphine.
23. The composition of claim 14 , wherein the poly(DL-lactide-co-glycolide) copolymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer.
24. The method of claim 11 , comprising subcutaneously administering the composition to the patient once per month.
25. The method of claim 12 , comprising subcutaneously administering the composition to the patient once per month.
26. The method of claim 13 , comprising subcutaneously administering the composition to the patient once per month.
27. The method of claim 15 , comprising subcutaneously administering the composition to the patient once per month.
28. An injectable composition comprising: (i) 8 wt % to about 22 wt % of buprenorphine free base; (ii) 15 wt % to about 50 wt % of a poly(DL-lactide-co-glycolide) copolymer having an average molecular weight of about 5,000 Daltons to about 40,000 Daltons; and (iii) 30 wt % to 70 wt % of N-methyl-2-pyrrolidone.
29. The composition of claim 28 , wherein the composition is transformed in situ into an implant by contact with a bodily fluid.
30. The composition of claim 28 , wherein the copolymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer.
31. The composition of claim 28 , wherein the copolymer has an average molecular weight of 5,000 Daltons to 40,000 Daltons.
32. The composition of claim 28 , wherein the copolymer has a carboxy terminal group.
33. The composition of claim 28 , wherein the weight ratio of buprenorphine to copolymer is between about 0.01:1 and about 2:1.
34. A method for treating opioid dependency in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the composition of claim 28 to treat the opioid dependency.
35. The method of claim 34 , comprising subcutaneously administering the composition to the patient once per month.
36. The composition of claim 28 , wherein the composition comprises from 3 milligrams to about 300 milligrams of the buprenorphine.
37. The composition of claim 1 , comprising from 20 wt % to 70 wt % of the poly(DL-lactide-co-glycolide) copolymer.
38. The composition of claim 5 , comprising from 20 wt % to 70 wt % of the poly(DL-lactide-co-glycolide) copolymer.
39. The composition of claim 10 , comprising from 20 wt % to 70 wt % of the poly(DL-lactide-co-glycolide) copolymer.
40. The composition of claim 14 , comprising from 20 wt % to 70 wt % of the poly(DL-lactide-co-glycolide) copolymer.
41. An injectable pharmaceutical composition comprising:
(i) 8 wt % to about 30 wt % of buprenorphine in the form of a free base or a pharmaceutically acceptable salt;
(ii) 5 wt % to about 70 wt % of a poly(lactide-co-glycolide) copolymer; and
(iii) 10 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
42. The composition of claim 41 , comprising about 8 wt % to about 22 wt % of the buprenorphine in the form of the free base or the pharmaceutically acceptable salt.
43. The composition of claim 41 , comprising about 15 wt % to 70 wt % of the poly(lactide-co-glycolide) copolymer.
44. The composition of claim 41 , comprising 15 wt % to about 50 wt % of the poly(lactide-co-glycolide) copolymer.
45. The composition of claim 41 , comprising 3 mg to about 300 mg of buprenorphine in the form of the free base or the pharmaceutically acceptable salt.
46. The composition of claim 41 , wherein the polymer is a 50/50 poly(lactide-co-glycolide) copolymer, a 55/45 poly(lactide-co-glycolide) copolymer, a 60/40 poly(lactide-co-glycolide) copolymer, a 65/35 poly(lactide-co-glycolide) copolymer, a 70/30 poly(lactide-co-glycolide) copolymer, a 75/25 poly(lactide-co-glycolide) copolymer, an 80/20 poly(lactide-co-glycolide) copolymer, an 85/15 poly(lactide-co-glycolide) copolymer, a 90/10 poly(lactide-co-glycolide) copolymer, or a 95/5 poly(lactide-co-glycolide) copolymer.
47. The composition of claim 41 , wherein the polymer is a 50/50 poly(lactide-co-glycolide) copolymer.
48. The composition of claim 41 , wherein the polymer is a 75/25 poly(lactide-co-glycolide) copolymer or an 85/15 poly(lactide-co-glycolide) copolymer.
49. The composition of claim 41 , consisting of (i), (ii), and (iii).
50. The composition of claim 41 having a 24 hour burst release of less than 10%.
51. The composition of claim 41 , wherein the poly(lactide-co-glycolide) copolymer has an average molecular weight from about 5,000 Daltons to about 20,000 Daltons.
52. The composition of claim 41 , wherein the buprenorphine is in the form of the free base.
53. A method for treating opioid addiction in a human in need thereof comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 41 to the human to treat the opioid addiction.
54. The method of claim 53 , wherein the composition is administered once per month by subcutaneous injection.
55. The method of claim 53 , wherein the composition is administered once every three months by subcutaneous injection.
56. The method of claim 53 , wherein the therapeutically effective amount of the buprenorphine in the form of the free base or the pharmaceutically acceptable salt is from 3 mg to about 300 mg.
57. The method of claim 53 , wherein the therapeutically effective amount of the buprenorphine in the form of the free base or the pharmaceutically acceptable salt is from 9 mg to about 900 mg.
58. A method for treating pain in a human in need thereof comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 41 to the human to treat the pain.