SUSTAINED-RELEASE NALTREXONE MICROCAPSULES

THE OBJECTIVE OF THIS PROJECT IS TO DEVELOP SUSTAINED-ACTION, INJECTABLE, BIODEGRADABLE, NALTREXONE MICROCAPSULES TO MAINTAIN PLASMA LEVELS AT 2 NG/ML FOR AT LEAST 1 MONTH. PHASE I SUPPORT IS SOUGHT FOR A 6-MONTH PERIOD TO CONDUCT PRELIMINARY FEASIBILITY STUDIES. DURING PHASE I, NALTREXONE MICROCAPSULES WILL BE PREPARED USING BIOTEK, INC.'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 BE ADMINISTERED TO RABBITS SO THAT PLASMA SAMPLES MAY BE OBTAINED DURING THE TIME COURSE OF RELEASE. THESE SAMPLES WILL BE PROVIDED TO NIDA FOR ANALYSIS. THESE PHASE I STUDIES WILL PROVIDE THE BASIS FOR FURTHER DEVELOPMENT DURING PHASE II WHEN THE FINAL PROTOTYPE FORMULATION WILL BE TESTED IN A VARIETY OF ANIMAL MODELS. PHARMACOKINETIC STUDIES WILL BE CONDUCTED AND DOCUMENTATION WILL BE PREPARED FOR AN IND APPLICATION.