Epilepsy is a debilitating disorder affecting 1 adult in 200 in the United States. Although several drugs are valuable for epilepsy therapy, their poor aqueous solubility does not permit effective formulation for intravenous administration. No IV formulation exists for carbamazepine (CBZ), a drug of choice for epilepsy therapy. Since therapeutic levels of CBZ in the brain are not reached for several hours following oral administration of this drug, other, less desirable drugs must be used when acute intervention during epileptic seizures is required. The objective of this proposal is to develop a formulation for carbamazepine suitable for intravenous administration. This will be accomplished using patented technology to convert this nearly water- insoluble drug into spherical, amorphous, uniformly-sized submicron particles suspended in a biocompatible aqueous medium. This technology has been applied successfully to other compounds to produce formulations for improved diagnostic imaging as well as for antI-cancer and antimicrobial therapy. Nanoparticle formulations have also demonstrated improved bioavailability following oral administration. Other administration routes may benefit as well. The intravenous formulation of carbamazepine will be subjected to preliminary pharmacokinetic and biodistribution evaluations to demonstrate feasibility. Phase Il objectives will focus on preclinical efficacy and toxicity studies. A phase Ill partner will be sought to conduct clinical trials for NDA submissions and marketing.
