Development of carbamazepine transnasal microemulsion for treatment of epilepsy

Carbamazepine is widely preferred therapy for the treatment of epilepsy. However, oral therapy results in slower brain uptake and systemic side effects. Intranasal route can achieve faster brain uptake, but poor aqueous solubility of carbamazepine is the main obstacle for administration by nasal route. The purpose of this study was to prepare and evaluate intranasal oil in water microemulsion of carbamazepine to improve its solubility and enhance the brain uptake. Intranasal microemulsion of carbamazepine was prepared by water titration method using oleic acid as oil, Tween 80 as surfactant and Transcutol® as cosurfactant. Microemulsions were evaluated for various physical parameters including globule size, viscosity, pH and conductivity. Toxicity study of microemulsion was carried out by employing sheep nasal mucosa. The microemulsion was also evaluated by maximal electric shock, and the brain uptake study was done using HPLC method. The microemulsion was stable and transparent with average globule size of 21.03 nm and did not show any toxic symptoms. It showed reduction in the hind limb extension phase and faster recovery from seizures in comparison to oral microemulsion and nasal solution. Higher brain/plasma ratio was obtained with nasal microemulsion in comparison to ratio obtained after intraperitoneal injection of carbamazepine solution.