A 30-DAY SUSTAINED RELEASE INJECTION OF CLONAZEPAM

EPILEPSY IS A FAMILY OF RECURRENT SEIZURE DISORDERS AFFLICTING 1-2 MILLION PEOPLE IN THE U.S. ALONE. ALTHOUGH THE ANTIEPILEPTIC DRUG DEVELOPMENT PROGRAM OF NINDS HAS EFFECTIVELY FOSTERED THE DEVELOPMENT OF NEW ANTICONVULSANT DRUGS, THERE REMAIN SIGNIFICANT LIMITATIONS IN METHODS AVAILABLE FOR ANTIEPILEPTIC DRUG DELIVERY, NOMELY BY MOUTH OR INJECTION. INJECTIONS ARE NOT WELL SUITED FOR CHRONIC SELF-ADMINISTRATION, ORAL MEDICATION IS OFTEN IMPOSSIBLE FOR YOUNG OR MENTALLY IMPAIRED PATIENTS, AND BOTH ROUTES ARE SUSCEPTIBLE TO NONCOMPLIANCE. WE WILL DEVELOP A 30 DAY INJECTABLE DEPOT FORM OF CLONAZEPAM, A DRUG ALREADY APPROVED AS A CHRONIC ANTICONVULSANT, USING MICROCAPSULES MADE OF POLY(LACTIDE-CO-GLYCOLIDE) MATERIALS. THESE COPOLYMERS ARE KNOWN TO DEGRADE IN VIVO, AT CONTROLLABLE RATE, INTO HARMLESS BYPRODUCTS. PHASE I WILL INCLUDE PREPARATION AND CHARACTERIZATION OF MICROCAPSULES IN VARIOUS SIZES AND DRUG LOADINGS, DETERMINATION OF IN VITRO RELEASE PROFILES, INVESTIGATION OF PHARMACOKINETICS IN RABBITS, AND SELECTION OF AN OPTIMUM FORMULATION. A SUBSEQUENT PHASE II PROGRAM WILL THEN SEEK FDA APPROVAL AND PURSUE COMMERCIALIZATION.