Claims for Patent: 11,110,084

Summary for Patent: 11,110,084

Title:	Opioid formulations
Abstract:	A depot precursor formulation comprising: a) a controlled-release matrix; b) at least oxygen containing organic solvent; c) at least 12% by weigh of at least one active agent selected from buprenorphine and salts thereof, calculated as buprenorphine free base. Corresponding depot compositions and methods of treatment in pain management, by opioid maintenance and related methods are provided.
Inventor(s):	Fredrik Tiberg, Ian Harwigsson, Markus Johnsson
Assignee:	Camurus AB
Application Number:	US17/142,673
Patent Claims:	1. A depot precursor formulation comprising: a) a lipid controlled release formulation comprising i) phosphatidylcholine and ii) glycerol dioleate, wherein the phosphatidylcholine is about 10 to about 25% by weight of the total weight of the depot precursor formulation, and the glycerol dioleate is about 15 to about 25% by weight of the total weight of the depot precursor formulation; b) about 25 to about 32% by weight of N-methyl-2-pyrrolidone; and c) about 25 to about 50% by weight of buprenorphine. 2. The depot precursor formulation of claim 1, wherein the depot precursor formulation is contained in a pre-filled syringe. 3. The depot precursor formulation of claim 2, wherein the depot precursor formulation within the pre-filled syringe comprises 40 to 140 mg of buprenorphine (calculated as a free base). 4. The depot precursor formulation of claim 1, wherein the depot precursor formulation has a viscosity that is about 1 to about 1000 mPas at 20° C. as measured with a CarriMed CSL 100 rheometer equipped with automatic gap setting. 5. The depot precursor formulation of claim 1, characterized in that the depot precursor formulation, when administered to a patient, exhibits a variation between Cmin and Cmax of buprenorphine at steady-state administration that is between 0.4 ng/mL and 10 ng/mL. 6. The depot precursor formulation of claim 1, wherein the depot precursor formulation, after contact with an aqueous fluid, forms a liquid crystalline phase structure. 7. The depot precursor formulation of claim 6, wherein the liquid crystalline phase structure is a non-lamellar crystalline phase structure. 8. The depot precursor formulation of claim 1, wherein the depot precursor formulation comprises: about 35% by weight of buprenorphine; about 14% by weight of a phosphatidylcholine; about 21% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. 9. The depot precursor formulation of claim 1, wherein the depot precursor formulation comprises: about 35% by weight of buprenorphine; about 17.5% by weight of a phosphatidylcholine; about 17.5% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. 10. The depot precursor formulation of claim 1, wherein the depot precursor formulation comprises: about 30% by weight of buprenorphine; about 25% by weight of a phosphatidylcholine; about 25% by weight of glycerol dioleate; and about 20% by weight of N-methyl-2-pyrrolidone. 11. The depot precursor formulation of claim 1, wherein the depot precursor formulation comprises: about 30% by weight of buprenorphine; about 16% by weight of a phosphatidylcholine; about 24% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. 12. A method of administering an opioid maintenance treatment to a subject, the method comprising administering a depot precursor formulation once monthly to the subject, wherein the depot precursor formulation comprises: a) a lipid controlled release formulation comprising i) phosphatidylcholine and ii) glycerol dioleate, wherein the phosphatidylcholine is about 10 to about 25% by weight of the total weight of the depot precursor formulation, and the glycerol dioleate is about 15 to about 25% by weight of the total weight of the depot precursor formulation; b) about 25 to about 32% by weight of N-methyl-2-pyrrolidone; and c) about 25 to about 50% by weight of buprenorphine. 13. The method of claim 12, wherein the depot precursor formulation is administered from a pre-filled syringe. 14. The method of claim 13, wherein the pre-filled syringe contains less than 1 mL of the depot precursor formulation. 15. The method of claim 14, wherein the depot precursor formulation comprises 40 to 140 mg of buprenorphine (calculated as a free base). 16. The method of claim 13, wherein the pre-filled syringe comprises a needle having a gauge greater than 18 G. 17. The method of claim 13, wherein the pre-filled syringe further comprises a needle stick prevention safety device. 18. The method of claim 13, wherein the pre-filled syringe is disposable. 19. The method of claim 12, wherein the depot precursor formulation provides a variation between Cmin and Cmax of buprenorphine at steady-state administration that is between 0.4 ng/mL and 10 ng/mL. 20. The method of claim 12, wherein the patient suffers from an opioid dependency. 21. The method of claim 12, wherein the patient suffers from opioid withdrawal. 22. The method of claim 12, wherein administering the opioid maintenance treatment treats pain in the patient. 23. The method of claim 12, wherein the patient is receiving or has previously received an oral dosage form comprising buprenorphine. 24. The method of claim 13, wherein the oral dosage form is sublingual. 25. The method of claim 12, wherein the depot precursor formulation, after contact with an aqueous fluid, forms a liquid crystalline phase structure. 26. The method of claim 15, wherein the liquid crystalline phase structure is a non-lamellar crystalline phase structure. 27. The method of claim 12, wherein the depot precursor formulation comprises: about 35% by weight of buprenorphine; about 14% by weight of a phosphatidylcholine; about 21% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. 28. The method of claim 12, wherein the depot precursor formulation comprises: about 35% by weight of buprenorphine; about 17.5% by weight of a phosphatidylcholine; about 17.5% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone. 29. The method of claim 12, wherein the depot precursor formulation comprises: about 30% by weight of buprenorphine; about 25% by weight of a phosphatidylcholine; about 25% by weight of glycerol dioleate; and about 20% by weight of N-methyl-2-pyrrolidone. 30. The method of claim 12, wherein the depot precursor formulation comprises: about 30% by weight of buprenorphine; about 16% by weight of a phosphatidylcholine; about 24% by weight of glycerol dioleate; and about 30% by weight of N-methyl-2-pyrrolidone.