Sustained release parenteral formulations of buprenorphine
View Patent ↗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- and pH-controlled buprenorphine-release formulation consisting of buprenorphine; a pH adjusting agent; and a surfactant that emulsifies said buprenorphine in oil, wherein the pH adjusting agent is NaOH, wherein the concentration of oil is from about 5% to about 20% and the pH of the formulation is from about 5.02 to about 8.06.
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. An oil- and pH-controlled buprenorphine-release formulation consisting of buprenorphine; a pH adjusting agent; glycerol; a buffer further selected from the group consisting of sodium citrate and sodium phosphate, and combinations thereof; preservatives selected from the group consisting of EDTA, benzyl alcohol, methyl paraben, propyl paraben, and combinations thereof; and a surfactant that emulsifies said buprenorphine in oil, wherein the pH adjusting agent is NaOH, wherein the concentration of oil is from about 5% to about 20% and the pH of the formulation is from about 5.02 to about 8.06 correspond to a desired release profile of the formulation.
6. The formulation according to claim 1 , 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.
7. The formulation according to claim 1 , wherein said suspending agent is selected from the group consisting of polyvinyl pyrrolidone (PVP), sodium carboxymethylcellulose, and dextran.
8. The formulation according to claim 1 , wherein the composition has a pH of from about 6 to about 8.
9. The formulation according to claim 1 , 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.
10. The formulation of claim 1 , wherein the combination of the concentration of oil and the pH is selected from the group consisting of 5% oil and pH 5.02; 10% oil and pH 5.30; 20% oil and pH 5.79; 5% oil and pH 7.92; 10% oil and pH 8.06; and 20% oil and pH 7.81.