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.

1 - 30 . (canceled) 
     
     
         31 . A depot precursor formulation comprising:
 a) a controlled-release polymer matrix comprising a biodegradable polymer, wherein the biodegradable polymer comprises a polyester and/or a polyamide;   b) at least one oxygen containing organic solvent; and   c) greater than 12% 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 and/or a sulfoxide.   
     
     
         32 . The depot precursor formulation of  claim 31  wherein the biodegradable polymer comprises at least one of a polylactate, a polyglycolate, a polylactate/glycolate copolymer, and mixtures thereof. 
     
     
         33 . The depot precursor formulation of  claim 31  wherein the polymer matrix comprises homopolymers, copolymers, or mixtures of homopolymers and copolymers. 
     
     
         34 . The depot precursor formulation of  claim 31  wherein the polymer is in the form of a molecular solution. 
     
     
         35 . The depot precursor formulation of  claim 31  wherein the polymer is in the form of microspheres in suspension. 
     
     
         36 . The depot precursor formulation of  claim 31  wherein the controlled release matrix comprises polylactate-co-glycolate (PLGA) microspheres. 
     
     
         37 . The depot precursor formulation of  claim 31  wherein at least 50% of component b) is N-methyl-2-pyrrolidone (NMP) and component c) is present at a level of 31 to 55% by weight, calculated as buprenorphine free base. 
     
     
         38 . The depot precursor formulation of  claim 31  wherein component c) is present at a level of 31 to 45% by weight buprenorphine, calculated as buprenorphine free base. 
     
     
         39 . The depot precursor formulation of  claim 31  comprising 40 to 70% by weight component b). 
     
     
         40 . The depot precursor formulation of  claim 31  for once-monthly administration. 
     
     
         41 . The depot precursor formulation of  claim 31  having a dose in the range 10 to 200 mg buprenorphine, calculated as buprenorphine free base. 
     
     
         42 . The depot precursor formulation of  claim 31  having a dose in the range 20 to 200 mg buprenorphine, calculated as buprenorphine free base. 
     
     
         43 . The depot precursor formulation of  claim 31  having a dose in the range 40 to 140 mg buprenorphine, calculated as buprenorphine free base. 
     
     
         44 . The depot precursor formulation of  claim 31  in ready-to-administer form. 
     
     
         45 . A method of treatment or prophylaxis of a human or non-human animal subject comprising administration of a precursor formulation of  claim 31 . 
     
     
         46 . A method of  claim 45  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. 
 
     
     
         47 . A method of transitioning a subject from a daily sublingual buprenorphine dose to a sustained buprenorphine formulation, comprising administering to said subject a monthly buprenorphine depot precursor formulation of  claim 31 , comprising 0.5 to 3 times the subject's previous daily buprenorphine dose. 
     
     
         48 . A depot precursor formulation comprising:
 a) a controlled-release polymer matrix comprising a biodegradable polymer, wherein the biodegradable polymer comprises a polyester and/or a polyamide;   b) at least one oxygen containing organic solvent; and   c) at least 30% 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.   
     
     
         49 . The depot precursor formulation of  claim 48  wherein component b) comprises at least one of N-methyl-2-pyrrolidone (NMP), dimethyl formamide (DMF) and dimethyl acetamide (DMA). 
     
     
         50 . A depot precursor formulation comprising:
 a) a lipid controlled release matrix;   b) at least oxygen containing organic solvent;   c) at least 12% by weight of at least one active agent selected from buprenorphine and salts thereof, calculated as buprenorphine free base;   wherein component b) comprises a sulfoxide.   
     
     
         51 . 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.   
     
     
         52 . A method of treatment or prophylaxis of a human or non-human animal subject comprising administration of a precursor formulation of  claim 51 . 
     
     
         53 . A method of  claim 52  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. 
 
     
     
         54 . A method of transitioning a subject from a daily sublingual buprenorphine dose to a sustained buprenorphine formulation, comprising administering to said subject a monthly buprenorphine depot precursor formulation of  claim 51  comprising 0.5 to 3 times the subject's daily sublingual buprenorphine dose. 
     
     
         55 . A method of sustained delivery of buprenorphine to a human or non-human animal body, said method comprising administering to the human or non-human animal body the depot precursor formulation of  claim 51 . 
     
     
         56 . A method for the formation of a depot composition comprising exposing the depot precursor formulation of  claim 51  to an aqueous fluid in vivo.