Claims for Patent: 9,937,164

Summary for Patent: 9,937,164

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):	Tiberg Fredrik, Harwigsson Ian, Johnsson Markus
Assignee:	Camurus AB
Application Number:	US14416421
Patent Claims:	1. A depot precursor formulation comprising:a) a lipid controlled release formulation comprising i) at least one neutral diacyl lipid; and ii) at least one phospholipid, wherein a weight ratio of i):ii) is from 90:10 to 20:80;b) 20-40% by weight of at least one oxygen containing organic solvent;c) at least 25% by weight of at least one active agent selected from buprenorphine and salts thereof, calculated as buprenorphine free base;wherein component b) comprises an amide.2. The depot precursor formulation of which forms a depot composition upon administration to the body of a subject.3. The depot precursor formulation of claim 1 , wherein the at least one active agent selected from buprenorphine and salts thereof is present at a level of greater than 30% by weight buprenorphine claim 1 , calculated as buprenorphine free base.4. The depot precursor formulation of claim 1 , wherein the at least one active agent selected from buprenorphine and salts thereof is present at a level of 31% to 45% by weight buprenorphine claim 1 , calculated as buprenorphine free base.5. The depot precursor formulation of claim 1 , wherein component i) comprises at least 50% by weight components with C16 to C18 acyl groups claim 1 , the C16 to C18 acyl groups having zero claim 1 , one or two unsaturations.6. The depot precursor formulation of claim 1 , wherein component ii) comprises at least 50% by weight components with C16 to C18 acyl groups claim 1 , the C16 to C18 acyl groups having zero claim 1 , one or two unsaturations.7. The depot precursor formulation of claim 5 , wherein component ii) comprises at least 50% by weight components with C16 to C18 acyl groups claim 5 , the C16 to C18 acyl groups having zero claim 5 , one or two unsaturations.8. The depot precursor formulation of claim 1 , wherein component b) comprises N-methyl-2-pyrrolidone.9. The depot precursor formulation of claim 1 , wherein component c) comprises buprenorphine as a free base.10. The depot precursor formulation of for once-monthly administration.11. The depot precursor formulation of having a dose in the range 10 to 200 mg buprenorphine claim 1 , calculated as free base.12. The depot precursor formulation of claim 1 , wherein the precursor formulation is in ready-to-administer form.13. The depot precursor formulation of claim 1 , wherein the precursor formulation is stable to storage in ready-to-administer form.14. A depot composition formed by administration to a human subject a depot precursor formulation of .15. The depot composition of which provides a Cmax (maximum concentration) in the blood plasma of said subject after a single administration of no more than 0.3 ng/ml per mg of administered buprenorphine.16. The depot composition of which provides a Cmax (maximum concentration) in the blood plasma of said subject after a single administration of no more than 0.17 ng/ml per mg of administered buprenorphine.17. The depot composition of claim 15 , wherein there is a linear relationship between the dose of buprenorphine administered to the subject and the AUC dose experienced by the subject.18. The depot composition of which claim 14 , upon administration to said subject claim 14 , provides a buprenorphine blood plasma profile not having any lag phase.19. The depot composition of claim 14 , wherein claim 14 , following administration to said subject of said depot precursor formulation once monthly for at least 6 months claim 14 , Cmin (minimum concentration) and Cmax (maximum concentration) at a steady-state both fall between 0.4 ng/mL and 10 ng/mL.20. The depot composition of claim 14 , wherein claim 14 , following administration to said subject of said depot precursor formulation once monthly for at least 6 months claim 14 , Cmin (minimum concentration) and Cmax (maximum concentration) at a steady-state both fall between 0.2 ng/mL and 2 ng/mL.23. A method of treatment or prophylaxis of a human or non-human animal subject comprising administration of a precursor formulation of .24. A method of for:(i) the treatment of pain or the treatment of opioid dependence by at least one of: detoxification and maintenance;(ii) opioid maintenance therapy by at least one of: detoxification and maintenance; or(iii) the treatment or prophylaxis of the symptoms of at least one of: opioid withdrawal and cocaine withdrawal.25. A method of transitioning a subject from a daily sublingual buprenorphine dose to a sustained buprenorphine formulation claim 1 , comprising administering to said subject a monthly buprenorphine depot precursor formulation of claim 1 , comprising 0.5 to 3 times the subject's daily sublingual buprenorphine dose.26. The depot precursor formulation of claim 8 , wherein component b) consists essentially of N-methyl-2-pyrrolidone.27. The depot precursor formulation of claim 1 , wherein the formulation comprises between 20-35% by weight of component b).28. The depot precursor formulation of claim 27 , wherein the formulation comprises between 25-32% by weight of component b).