During the SBIR Phase I contract period, we established the feasibility of developing sustained release injectable microsphere formulation from clonazepam and biodegradable FDA approved polylactide-co-glycolide polymers. The microspheres demonstrated a steady state release of the drug from seven to ten days in vivo in rabbits. The duration of release depended on the type of microspheres, microsphere size, and the type of polymer use in their preparation. For the SBIR Phase II contract period, we propose to continue this important development and to evaluate the safety and pharmacokinetics of release of at least a seven day injectable microsphere formulation in animals and in human volunteers. We will first confirm the preparation of the seven to ten day microsphere formulation, and characterize its physical, chemical and in vitro release properties. After this is completed, and before initiating human testing, we will test the safety and pharmacokinetics of the seven-day formulation in vivo in rabbits. Finally, the formulation will be tested in healthy human volunteers to determine the pharmacokinetics of release of the drug in humans.
