Buprenorphine is a semisynthetic opioid derived from thebaine. It has long lasting analgesic action at low doses with little clinically significant dependence liability or serious toxicity. Buprenorphine suppresses heroin intake by heroin addicts and has opiate antagonist activity similar to naltrexone. Recently, buprenorphine has been reported to be effective in the detoxification of heroin addicts. Because of these properties, buprenorphine possesses distinct advantages over methadone or naltrexone as a safe and highly effective drug for the treatment of opiate dependence. A one month sustained action microcapsule injectable formulation would improve the cost effectiveness of the treatment by reducing several visits per week to one per month. The level of compliance may also be improved by a reduction in the number of visits. More significantly, sustained action buprenorphine will permit more flexible scheduling of other therapeutic interventions, and drug seeking/taking behavior will no longer be a part of the post addicts daily life. This may well contribute to increased efficacy and reduced recidivism. During the Phase I SBIR grant period, several biodegradable microcapsule formulations were developed which maintained a sustained blood plasma level of buprenorphine in rabbits for one month. Support is now being requested for Phase II development for a period of two years. During this period microcapsule development will be completed; all preclinical studies required by the FDA will be conducted; manufacturing specifications, processes and controls will be documented; IND application will be filed with the FDA; and the microcapsules for clinical studies will be manufactured. The IND documentation and the microcapsules will be submitted to NIDA for use in its contemplated clinical trials during Phase II.
