WO 2008/106571 A2 - Sustained Release Parenteral Formulations Of Buprenorphine - The Lens

Sustained Release Parenteral Formulations Of Buprenorphine

Published: Sep 4, 2008
Earliest Priority: Feb 28 2007
Family: 5
Cited Works: 0
Cited by: 1
Cites: 0
Additional Info: Full text

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.

Claims

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.
The formulation according to claim 1 wherein said buprenorphine is selected from the group consisting of a free base and a salt.
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.
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.
The formulation according to claim 1 further comprising glycerol.
The formulation according to claim 1 further comprising pH adjusting agents selected from the group consisting of sodium hydroxide.
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.
The formulation according to claim 1 further comprising preservatives selected from the group consisting of benzyl alcohol, EDTA, and combinations thereof.
A buprenorphine aqueous suspension formulation comprising free base buprenorphine and a suspending agent.
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.
The formulation according to claim 9, wherein said suspending agent is selected from the group consisting of polyvinyl pyrrolidone (PVP), sodium carboxymethylcellulose, and dextran.
The formulation according to claim 9, wherein the composition has a pH of from about 6 to about 8.
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.
The formulation according to claim 9 further comprising preservatives selected from the group consisting of benzyl alcohol, methyl paraben, propyl paraben, and combinations thereof.
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.
A buprenorphine oil formulation comprising a buprenorphine salt suspended in a pharmaceutically acceptable oil.
The formulation according to claim 15, wherein said buprenorphine salt is buprenorphine HCl.
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.
The formulation according to claim 15 further comprising a suspending agent as a sorbitan fatty acid hexitan ester.
A method of providing sustained release of buprenorphine over a period of time by administering the formulation according to claims 1, 9, and 16.