Development of Valproic acid niosomal in situ nasal gel formulation for epilepsy

Abstract

Valproic acid is an anti-epileptic drug used in the treatment of epilepsy and seizures. The study was designed with three aims. Firstly, to enhance the solubility and bioavailability of BCS class II drug Valproic acid; secondly, to ease administration of the formulation to the epileptic patient, during an attack, and thirdly, to reduce the dose of drug for long-term treatment. In the culmination of this study, an anti-epileptic drug loaded (Valproic acid) niosomal gel for nose-to-brain-delivery using thermosensitive polymer PF 127 was formulated, which can be a controlled dose to the patient. Niosomal formulations were optimized by altering the proportions of range of Tween and Span. The formulations were prepared by ether injection method. The formulation was then evaluated for morphological characterization, encapsulation efficiency, and viscosity. Valproic acid niosomes formulated with Tween 80 and Span 60 were found to entrap high amounts of drug. Further the niosomal gel was prepared by using various concentrations of PF 127 and were optimized at effective concentrations and studied for gelation temperature, melting temperature and heat of enthalpies, mucoadhesive strength, gel strength and showed satisfactory results. The niosomes entrapped in-situ nasal gel formulations showed sufficient quantity of in-vitro drug release through the gel across the goat's nasal mucosa. In histopathological study no effect of surfactant was seen; neither had the formulations caused any damage to the nasal tissue. Hence we can conclude that the niosomal in-situ nasal gel system can be considered as a promising approach for the anti-epileptic drug Valproic Acid.