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. A method for treating opioid dependence in a subject in need thereof, the method comprising administering to the subject by subcutaneous injection a therapeutically effective amount of a pharmaceutical composition comprising:
(i) 10 wt % to about 50 wt % of buprenorphine free base;
(ii) 5 wt % to about 70 wt % of a poly(lactide-co-glycolide) copolymer; and
(iii) N-methyl-2-pyrrolidone; to treat the opioid dependence.
2. The method of claim 1 , comprising administering the composition once every twenty-eight days.
3. The method of claim 1 , comprising administering the composition once per month.
4. The method of claim 1 , wherein the composition comprises from 10 wt % to about 30 wt % of the buprenorphine free base.
5. The method of claim 1 , wherein the composition comprises from about 15 wt % to about 20 wt % of the buprenorphine free base.
6. The method of claim 1 , wherein the composition comprises about 18 wt % of the buprenorphine free base.
7. The method of claim 1 , wherein the composition comprises from about 15 wt % to about 70 wt % of the poly(lactide-co-glycolide) copolymer.
8. The method of claim 1 , wherein the composition comprises about 32 wt % of the poly(lactide-co-glycolide) copolymer.
9. The method of claim 1 , wherein the poly(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(lactide-co-glycolide) copolymer.
10. The method of claim 1 , wherein the poly(lactide-co-glycolide) copolymer is a 50/50 poly(lactide-co-glycolide) copolymer.
11. The method of claim 1 , wherein the composition comprises from about 10 wt % to about 70 wt % of the N-methyl-2-pyrrolidone.
12. The method of claim 1 , wherein the composition comprises about 50 wt % of the N-methyl-2-pyrrolidone.
13. The method of claim 1 , wherein the poly(lactide-co-glycolide) copolymer has an average molecular weight from about 5,000 Daltons to about 40,000 Daltons.
14. The method of claim 1 , wherein the poly(lactide-co-glycolide) copolymer has an average molecular weight from about 10,000 Daltons to about 20,000 Daltons.
15. A method for treating opioid dependence in a patient, the method comprising administering to the patient, by subcutaneous injection, a pharmaceutical composition comprising about 18 wt % of buprenorphine free base, about 32 wt % of a poly(lactide-co-glycolide) copolymer, and about 50 wt % of N-methyl-2-pyrrolidone.
16. The method of claim 15 , wherein the composition is transformed in situ into an implant by contact with body fluid of the patient.
17. The method of claim 15 , wherein the composition provides sustained release of buprenorphine to the patient for at least 28 days.
18. The method of claim 15 , wherein the composition provides sustained release of buprenorphine to the patient for at least 45 days.
19. The method of claim 15 , wherein the composition provides sustained release of buprenorphine to the patient for at least 60 days.
20. The method of claim 15 , wherein the pharmaceutical composition comprises about 3 mg to about 300 mg of the buprenorphine free base; and wherein the composition has a volume of about 0.5 mL.
21. The method of claim 15 , wherein the pharmaceutical composition comprises about 9 mg to about 900 mg of the buprenorphine free base; and wherein the composition has a volume of about 1.5 mL.
22. The method of claim 15 , wherein the poly(lactide-co-glycolide) copolymer is a 50:50 poly(lactide-co-glycolide) copolymer.
23. The method of claim 15 , wherein the poly(lactide-co-glycolide) copolymer is a 50:50 poly(lactide-co-glycolide) copolymer having an average molecular weight of about 5,000 Daltons to about 40,000 Daltons.
24. The method of claim 15 , wherein the poly(lactide-co-glycolide) copolymer is a 50:50 poly(lactide-co-glycolide) copolymer having a carboxy terminal group and an average molecular weight of about 10,000 Daltons to about 20,000 Daltons.
25. The method of claim 15 , wherein the buprenorphine composition comprises from about 3 mg to about 300 mg of buprenorphine free base.
26. A method for treating opioid dependence in a patient in need thereof, the method comprising subcutaneously administering a buprenorphine composition to the patient once every two months; wherein the buprenorphine composition comprises about 18 wt % of buprenorphine free base; about 32 wt % of a poly(lactide-co-glycolide) copolymer; and about 50 wt % of N-methyl-2-pyrrolidone.
27. The method of claim 26 , wherein the poly(lactide-co-glycolide) copolymer is a 50:50 poly(lactide-co-glycolide) copolymer.
28. The method of claim 26 , wherein the poly(lactide-co-glycolide) copolymer is a 50:50 poly(lactide-co-glycolide) copolymer having an average molecular weight of about 5,000 Daltons to about 40,000 Daltons.
29. The method of claim 26 , wherein the poly(lactide-co-glycolide) copolymer is a 50:50 poly(lactide-co-glycolide) copolymer having a carboxy terminal group and an average molecular weight of about 10,000 Daltons to about 20,000 Daltons.
30. The method of claim 26 , wherein the buprenorphine composition comprises from about 3 mg to about 300 mg of buprenorphine free base.
31. A method for treating opioid dependence in a patient in need thereof, the method comprising subcutaneously administering a buprenorphine composition to the patient once every two months; wherein the buprenorphine composition comprises 10 wt % to about 50 wt % buprenorphine free base; 5 wt % to about 70 wt % of a poly(lactide-co-glycolide) copolymer; and N-methyl-2-pyrrolidone.
32. The method of claim 31 , wherein the buprenorphine composition comprises about 8 wt % to about 30 wt % of buprenorphine free base; about 5 wt % to about 70 wt % of the poly(lactide-co-glycolide) copolymer; and about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
33. The method of claim 32 , wherein the poly(lactide-co-glycolide) copolymer has an average molecular weight of about 5,000 Daltons to about 40,000 Daltons.
34. The method of claim 31 , wherein the buprenorphine composition comprises about 10 wt % to about 30 wt % of buprenorphine free base; about 15 wt % to about 70 wt % of the poly(lactide-co-glycolide) copolymer, and about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
35. The method of claim 34 , wherein the poly(lactide-co-glycolide) copolymer has an average molecular weight of about 5,000 Daltons to about 40,000 Daltons.