Buprenorphine has been shown to suppress heroin use by addicts and studies indicate that it may be a useful treatment for opioid dependence. This partial agonist-antagonist combines the advantages of both methadone and naltrexone, and buprenorphine was preferred by post addicts over methadone and naltrexone. The overall objective of this program is to develop during the next three years a sustained action formulation of microencapsulated buprenorphine which is effective for one month and to prepare documentation to support an IND application for initial clinical trials. Phase I SBIR support is sought to demonstrate the feasibility of the project. Injectable buprenorphine microcapsules will be prepared using BIOTEK's proprietary air suspension coating process and evaluated for in vitro drug release kinetics, drug content, surface morphology, residual solvent and size distribution. Pharmacokinetic studies will be utilized to determine in vivo release rates. In vivo and in vitro release rates will be compared and correlated to process variables such as type of polymer, microcapsule drug loading, coating level, and size distribution. In addition in vivo release rates will be correlated to injection vehicle and route of administration. Phase I studies will provide the methodological basis for further development of the formulation in Phase II. During Phase II the prototype development will be completed, efficacy and safety tests conducted, and manufacturing procedures defined to support an IND application in anticipation of human trials.
