Research Project
2270268
Epilepsy is a debilitating disorder affecting 1 person in 100 in the U.S. No intravenous formulation exists for carbamazepine (CBZ), a drug of choice for epilepsy therapy; potentially less desirable drugs must be used when enteral administration is not possible and for acute intervention during status epilepticus. This severe manifestation of epilepsy may affect as many as 25% of all epileptic children, and will leave a significant fraction of those affected with permanent neurological damage. Intervention requires the use of medication that can be administered either by injection, usually intravenously, or per rectum. The objective of this project is to develop a safe and efficacious formulation for carbamazepine suitable for IV administration. In Phase I a microparticle suspension of CBZ in a biocompatible acqueous medium was developed. In mice, IV administration of this formulation resulted in therapeutic levels of CBZ in plasma within 2 minutes. The evaluation of this microparticle formulation in Phase II will include: (1) thorough pharmacokinetics and biodistribution studies in the mouse and rat, (2) neurotoxicity determination in the mouse; (3) efficacy evaluation in standard anticonvulsant mouse models; and (4) efficacy demonstration in a rat model of status epilepticus. In addition, the microparticle CBZ formulation manufacturing process will be scaled up in preparation for clinical trials in Phase III. Successful completion of this project will provide an intravenous formulation for the treatment of status epilepticus and should improve bioavailability when administered per os or per rectum; we believe the probability of commercial success is high. PROPOSED COMMERCIAL APPLICATION: Medisperse, a five-year old company formed to commercialize a patented technology developed by the P.I. and funded through the SBIR program, currently produces nanoparticle drug formulations for client marketing. We believe this technology can significantly improve intravenous epilepsy therapy.
