ONE WEEK SUSTAINED RELEASE METHADONE MICROCAPSULES

THE OVERALL OBJECTIVE OF THE PROJECT IS TO DEVELOP SUSTAINED ACTION INJECTABLE BIODEGRADABLE L-METHADONE MICROCAPSULES WHICH WILL MAINTAIN PLASMA LEVELS OF 200 NG/ML FOR ONE WEEK. PHASE I SBIR SUPPORT IS SOUGHT FOR A SIX MONTH PERIOD TO CONDUCT PRELIMINARY FEASIBILITY STUDIES. DURING PHASE I METHADONE MICROCAPSULES WILL BE PREPARED FROMSEVERAL POLYMERS USING BIOTEK'S AIR SUSPENSION PROCESS. INITIAL EMPHASIS WILL BE PLACED ON PREPARING MICROCAPSULES FROM THREE DIFFERENT POLYMER COMPOSITIONS WHICH ARE AVAILABLE AT BIOTEK. THE EFFECT OF MICROCAPSULE WALL THICKNESS AND SIZE OF ON L-METHADONE RELEASE KINETICS WILL BE EVALUATED. MICROCAPSULES WILL BE EVALUATED FOR IN VITRO L-METHADONE RELEASE KINETICS, SURFACE MORPHOLOGY, SIZE DISTRIBUTION, ANDDRUG CONTENT. IN VIVO DURATION OF METHADONE RELEASE FROM THE SUSTAINED ACTION FORMULATION WILL BE STUDIED IN TWO SPECIES, RATS AND RABBITS. PHYSIOLOGICAL SIGNS OF OPIOID ACTION WILL BE OBSERVED IN RATS, AND INITIAL PHARMACOKINETICEVALUATION OF THE FORMULATION WILL BE STUDIED IN RABBITS. 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 MORE EXTENSIVE PHARMACOKINETIC STUDIES WILL BE CONDUCTED. DOCUMENTATION WILL BE PREPARED FOR AN IND APPLICATION.