Sustained release parenteral formulations of buprenorphine

Abstract

An oil-in-water buprenorphine formulation including buprenorphine and a surfactant that emulsifies the buprenorphine in oil, wherein the drug release is controlled by varying the oil concentration and/or pH. A buprenorphine aqueous suspension formulation including a free base buprenorphine and a suspension stabilizer. A buprenorphine oil formulation including a buprenorphine salt suspended in a pharmaceutically acceptable oil. Methods of providing sustained release of buprenorphine over a period of time.

1 . An oil-in-water buprenorphine formulation comprising buprenorphine: and a surfactant that emulsifies said buprenorphine in oil, wherein control of release of said buprenorphine is controlled by varying the oil concentration and/or pH. 
     
     
         2 . The formulation according to  claim 1 , wherein said buprenorphine is selected from the group consisting of a free base and a salt. 
     
     
         3 . The formulation according to  claim 1 , wherein said surfactant is selected from the group consisting of synthetic non-ionic surfactants, polypropylene polyethylene block copolymers, phosphatides, egg phosphatide, polysorbates, other surfactants acceptable for parenteral administration, and combinations thereof. 
     
     
         4 . The formulation according to  claim 1 , wherein said buprenorphine is dissolved in a water immiscible solvent selected from the group consisting of vegetable oil, soybean oil, safflower oil cottonseed oil, corn oil, sunflower oil, arachis oil, castor oil, olive oil, ester of a medium or long chain fatty acid such as a mono- di-, or triglyceride, ethyl oleate, isopropyl myristate, polyoxyl hydrogenated castor oil, and combinations thereof. 
     
     
         5 . The formulation according to  claim 1  further comprising glycerol. 
     
     
         6 . The formulation according to  claim 1  further comprising pH adjusting agents selected from the group consisting of sodium hydroxide. 
     
     
         7 . The formulation according to  claim 1  further comprising substances selected from the group consisting of a buffer further selected from the group consisting of sodium citrate and sodium phosphate, and combinations thereof. 
     
     
         8 . The formulation according to  claim 1  further comprising preservatives selected from the group consisting of benzyl alcohol, EDTA, and combinations thereof. 
     
     
         9 . A buprenorphine aqueous suspension formulation comprising free base buprenorphine and a suspending agent. 
     
     
         10 . The formulation according to  claim 9 , wherein said buprenorphine is a free base buprenorphine formed by the addition of an alkali metal salt selected from the group consisting of NaOH to buprenorphine salt. 
     
     
         11 . The formulation according to  claim 9 , wherein said suspending agent is selected from the group consisting of polyvinyl pyrrolidone (PVP) sodium carboxymethylcellulose, and dextran. 
     
     
         12 . The formulation according to  claim 9 , wherein the composition has a pH of from about 6 to about 8. 
     
     
         13 . The formulation according to  claim 9 , wherein said formulation further comprises substances selected from the group consisting of a buffer further selected from the group consisting of sodium citrate and sodium phosphate, and combinations thereof. 
     
     
         14 . The formulation according to  claim 9  further comprising preservatives selected from the group consisting of benzyl alcohol, methyl paraben, propyl paraben, and combinations thereof. 
     
     
         15 . The formulation according to  claim 9 , wherein said buprenorphine is a free base buprenorphine formed by dispersing said buprenorphine free base into the suspending agent solution and mixing the formulation with a high shear homogenizer. 
     
     
         16 . A buprenorphine oil formulation comprising a buprenorphine salt suspended in a pharmaceutically acceptable oil. 
     
     
         17 . The formulation according to  claim 15 , wherein said buprenorphine salt is buprenorphine HCl. 
     
     
         18 . The formulation according to  claim 15 , wherein said pharmaceutically acceptable oil is selected from the group consisting of cottonseed oil, corn oil, peanut oil, and soybean oil. 
     
     
         19 . The formulation according to  claim 15  further comprising a suspending agent as a sorbitan fatty acid hexitan ester. 
     
     
         20 . A method of providing sustained release of buprenorphine over a period of time by administering the formulation according to  claims 1 ,  9 , and  16 .