The overall objective of the project is to develop sustained action injectable maltrexone biodegradable microencapsules which will maintain plasma levels at 2 ng/ml for at least one month. Phase I SBIR support is sought for a six month period to conduct preliminary feasibility studies. During Phase I naltrexone microcapsules will be prepared using BIOTEK's air suspension process. This process produces true wall/reservoir microcapsules with zero order release characteristics. Microcapsules will be evaluated for in vitro release rates, surface morphology, drug content, and size distribution. The duration of antagonist release will be determined for several formulations and doses in rats using a simple observational screen test. The most promising formulation will administered to rabbits so that plasma samples may be obtained during the time course of release. These sample will be provided to NIDA for analysis. These Phase I studies will provide the basis for further development of the formulation in Phase II. The final prototype formulation will be tested in a variety of animal models, and pharmacokinetic studies will be conducted. Documentation will be prepared for an IND application.
