Injectable flowable composition 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 addiction in a human in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition to the human to treat the opioid addiction; wherein the pharmaceutical composition comprises:
(i) 8 wt % to about 30 wt % of buprenorphine in the form of the free base or a pharmaceutically acceptable salt;
(ii) about 20 wt % to about 70 wt % of a poly(DL-lactide-co-glycolide) copolymer; and
(iii) about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
2. The method of claim 1 , wherein the composition comprises from about 3 milligrams to about 300 milligrams of buprenorphine in the form of a free base or pharmaceutically acceptable salt.
3. The method of claim 1 , wherein the polymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer having an average molecular weight of about 5,000 Daltons to about 40,000 Daltons.
4. The method of claim 1 , wherein the polymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer having an average molecular weight of about 10,000 Daltons to about 20,000 Daltons.
5. The method of claim 1 , wherein the composition is transformed in situ into a solid implant after being parenterally administered to the human.
6. The method of claim 1 , wherein the composition consists of (i), (ii), and (iii).
7. The method of claim 1 , wherein the composition comprises
(i) 8 wt % to about 22 wt % of buprenorphine in the form of the free base;
(ii) about 25 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) about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
8. The method of claim 7 , wherein the composition consists of (i), (ii), and (iii).
9. The method of claim 1 , wherein the method comprises administering the pharmaceutical composition to the human once per month by injection.
10. The method of claim 1 , wherein the method comprises administering the pharmaceutical composition to the human once every three months by injection.
11. The method of claim 1 , wherein the method comprises administering the pharmaceutical composition to the human once every four months by injection.
12. The method of claim 1 , wherein the method comprises administering the pharmaceutical composition to the human once every six months by injection.
13. The method of claim 1 , wherein the pharmaceutical composition has a substantially linear release profile that lasts for 28 days after administration to the human.
14. The method of claim 1 , wherein the therapeutically effective dose of buprenorphine is delivered to the human for at least about 15 days after administration; for at least about 28 days after administration; for at least about 45 days after administration; or for at least about 60 days after administration.
15. The method of claim 1 , wherein the administration is a subcutaneous injection.
16. A method for treating opioid addiction in a human in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition to the human to treat the opioid addiction; wherein the pharmaceutical composition comprises:
(i) 8 wt % to about 30 wt % of buprenorphine in the form of a free base or pharmaceutically acceptable salt;
(ii) about 15 wt % to about 70 wt % of a biodegradable thermoplastic polymer; and
(iii) about 10 wt % to about 90 wt % of an organic liquid selected from the group consisting of N-methyl-2-pyrrolidone, 2-pyrrolidone, acetic acid, lactic acid, methyl lactate, ethyl lactate, monomethyl succinate acid, monomethyl citric acid, glycofurol, glycerol formal, isopropylidene glycol, 2,2-dimethyl-1,3-dioxolone-4-methanol, solketal, dimethylformamide, dimethylacetamide, dimethylsulfoxide, dimethylsulfone, epsilon-caprolactone, butyrolactone, caprolactam, or a mixture of two or more thereof.
17. The method of claim 16 , wherein the polymer is a polylactide, a polyglycolide, a polycaprolactone, a copolymer thereof, a terpolymer thereof, or any combination thereof.
18. A method for treating opioid addiction in a human in need thereof comprising subcutaneously injecting a pharmaceutical composition into the human once per month to treat the opioid addiction; wherein the pharmaceutical composition consists of:
(i) 8 wt % to about 22 wt % of buprenorphine in the form of a free base;
(ii) about 25 wt % to about 50 wt % of a poly(DL-lactide-co-glycolide) copolymer; and
(iii) about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone; and
wherein the composition comprises from about 3 milligrams to about 300 milligrams of the buprenorphine in the form of the free base.
19. A method for treating chronic pain in a human in need thereof comprising subcutaneously injecting a pharmaceutical composition into the human once per month to treat the chronic pain; wherein the pharmaceutical composition consists of:
(i) 8 wt % to about 22 wt % of buprenorphine in the form of a free base;
(ii) about 25 wt % to about 50 wt % of a poly(DL-lactide-co-glycolide) copolymer; and
(iii) about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone; and
wherein the composition comprises from about 3 milligrams to about 300 milligrams of buprenorphine in the form of the free base.
20. A method for treating pain in a human in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition to the human to treat the pain; wherein the pharmaceutical composition comprises:
(i) 8 wt % to about 30 wt % of buprenorphine in the form of the free base or a pharmaceutically acceptable salt;
(ii) about 20 wt % to about 70 wt % of a poly(DL-lactide-co-glycolide) copolymer; and
(iii) about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
21. The method of claim 20 , wherein the pain is chronic pain.
22. The method of claim 20 , wherein the composition comprises from about 3 milligrams to about 300 milligrams of buprenorphine in the form of a free base or pharmaceutically acceptable salt.
23. The method of claim 20 , wherein the polymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer having an average molecular weight of about 5,000 Daltons to about 40,000 Daltons.
24. The method of claim 20 , wherein the polymer is a 50/50 poly(DL-lactide-co-glycolide) copolymer having an average molecular weight of about 10,000 Daltons to about 20,000 Daltons.
25. The method of claim 20 , wherein the composition is transformed in situ into a solid implant after being parenterally administered to the human.
26. The method of claim 20 , wherein the composition consists of (i), (ii), and (iii).
27. The method of claim 20 , wherein the composition comprises
(i) 8 wt % to about 22 wt % of buprenorphine in the form of the free base;
(ii) about 25 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) about 30 wt % to about 70 wt % of N-methyl-2-pyrrolidone.
28. The method of claim 27 , wherein the composition consists of (i), (ii), and (iii).
29. The method of claim 20 , wherein the method comprises administering the pharmaceutical composition to the human once per month by injection.
30. The method of claim 20 , wherein the method comprises administering the pharmaceutical composition to the human once every three months by injection.
31. The method of claim 20 , wherein the administration is a subcutaneous injection.
32. A method for treating pain in a human in need thereof comprising administering a therapeutically effective amount of a pharmaceutical composition to the human to treat the pain; wherein the pharmaceutical composition comprises:
(i) 8 wt % to about 30 wt % of buprenorphine in the form of a free base or pharmaceutically acceptable salt;
(ii) about 15 wt % to about 70 wt % of a biodegradable thermoplastic polymer; and
(iii) about 10 wt % to about 90 wt % of an organic liquid selected from the group consisting of N-methyl-2-pyrrolidone, 2-pyrrolidone, acetic acid, lactic acid, methyl lactate, ethyl lactate, monomethyl succinate acid, monomethyl citric acid, glycofurol, glycerol formal, isopropylidene glycol, 2,2-dimethyl-1,3-dioxolone-4-methanol, solketal, dimethylformamide, dimethylacetamide, dimethylsulfoxide, dimethylsulfone, epsilon-caprolactone, butyrolactone, caprolactam, or a mixture of two or more thereof.
33. The method of claim 32 , wherein the polymer is a polylactide, a polyglycolide, a polycaprolactone, a copolymer thereof, a terpolymer thereof, or any combination thereof.
34. The method of claim 16 , wherein the composition consist of (i), (ii), and (iii).
35. The method of claim 32 , wherein the composition consist of (i), (ii), and (iii).