Development of a Naltrexone Microcapsule Injection

We will develop clinically useful naltrexone sustained release microcapsules for use in reducing re-addiction among recently withdrawn abusers. Naltrexone is an opiate antagonist which physiologically blocks the narcotic reinforcement mechanism. The microcapsules are targeted to contain more than 50% drug and to deliver approximately 5 mg/per day for one month. We previously developed injectable naltrexone microcapsules which produce opioid antagonism for 30 days or more in monkeys. Because the level of residual methylene chloride in those capsules exceeded the chronic exposure limit of the FDA, in this project a new microfluidized bed process recently developed will be used to greatly reduce the level of methylene chloride. The program will conduct research and development on the preparation of naltrexone microcapsules by the new process, including physical, physicochemical, and in vitro release evaluation. The best microcapsule formulation will be selected for use in Phase II pharmacological and toxicological testing in animals and subsequent human clinical tests.