Injectable flowable composition comprising buprenorphine
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 flowable composition comprising:
(i) 10 wt % to about 50 wt % of buprenorphine in the form of a free base or a pharmaceutically acceptable salt;
(ii) about 5 wt % to about 70 wt % of a poly(lactide-co-glycolide) copolymer; and
(iii) N-methyl-2-pyrrolidone.
2. The composition of claim 1 , comprising from 10 wt % to about 30 wt % of the buprenorphine.
3. The composition of claim 1 , comprising from about 15 wt % to about 20 wt % of the buprenorphine.
4. The composition of claim 1 , comprising from about 15 wt % to about 70 wt % of the poly(lactide-co-glycolide) copolymer.
5. The composition 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.
6. The composition of claim 1 , wherein the poly(lactide-co-glycolide) copolymer is a 50/50 poly(lactide-co-glycolide) copolymer.
7. The composition of claim 1 , wherein the buprenorphine is in the form of the free base.
8. The composition of claim 1 , comprising from about 3 mg to about 300 mg of the buprenorphine free base.
9. An injectable flowable 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.
10. The composition of claim 9 , wherein the poly(lactide-co-glycolide) copolymer has a carboxy terminal group.
11. The composition of claim 9 , wherein the poly(lactide-co-glycolide) copolymer has an average molecular weight from about 5,000 Daltons to about 20,000 Daltons.
12. The composition of claim 9 , 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 from about 5,000 Daltons to about 20,000 Daltons.
13. The composition of claim 9 , wherein the composition transforms in situ into an implant by contact with water, a bodily fluid, or other aqueous medium.
14. The composition of claim 9 , wherein the composition comprises from about 3 mg to about 300 mg of buprenorphine free base.
15. The composition of claim 14 having a volume of about 0.5 mL.
16. The composition of claim 9 , wherein the composition comprises from about 9 mg to about 900 mg of buprenorphine free base.
17. The composition of claim 16 having a volume of about 1.5 mL.
18. The composition of claim 9 having a volume from about 0.10 mL to about 2.0 mL.
19. A syringe comprising the composition of claim 9 .
20. A container comprising the composition of claim 9 .
21. An injectable flowable pharmaceutical composition comprising about 15 wt % to about 30 wt % of buprenorphine free base; about 5 wt % to about 50 wt % of a poly(lactide-co-glycolide) copolymer; and about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
22. The composition of claim 21 , wherein the composition transforms in situ into an implant by contact with water, a bodily fluid, or other aqueous medium.
23. The composition of claim 21 , wherein the biodegradable thermoplastic polymer is a poly(lactide-co-glycolide) copolymer having an average molecular weight of about 5,000 Daltons to about 20,000 Daltons.
24. An injectable flowable pharmaceutical composition comprising about 15 wt % to about 30 wt % of buprenorphine free base; about 5 wt % to about 50 wt % of a poly(lactide-co-glycolide) copolymer; and about 30 wt % to about 70 wt % of a biocompatible organic liquid comprising: (i) N-methyl-2-pyrrolidone and (ii) glycerin, propylene glycol, polyethylene glycol, or a combination of two or more thereof.
25. The composition of claim 24 , wherein the composition transforms in situ into an implant by contact with water, a bodily fluid, or other aqueous medium.
26. The composition of claim 21 , comprising about 18 wt % of buprenorphine free base.
27. The composition of claim 24 , comprising about 18 wt % of buprenorphine free base.
28. The container of claim 19 , wherein the composition transforms in situ into an implant by contact with water, a bodily fluid, or other aqueous medium.