Development of phenytoin intranasal microemulsion for treatment of epilepsy

Abstract

The objective of the present investigation was to prepare phenytoin microemulsion for intranasal administration by application of experimental design. Phenytoin microemulsion was prepared by water titration method. The concentration of oil (X1), surfactant (X2) and cosurfactant (X3) were selected as independent variables, in a simplex centroid design, from microemulsion region obtained from pseuodoternary phase diagram while the globule size (Y1) and cumulative phenytoin diffused at 60 min (Y2) through sheep nasal mucosa were taken as dependent variables. Mathematical models were generated for the response variables. The validity of the generated equations was established using check point batches. Microemulsion that had a smaller globule size of dispersed phase and high level of % drug diffusion was desirable. The generated mathematical equations were used to identify the desirable zone where all the criteria for the responses were satisfied and an optimum batch was recognized. Ex-vivo study of optimum microemulsion on sheep nasal mucosa shows absence of nasal toxicity. It was found that faster recovery from seizures was obtained in rats treated with intra nasal phenytoin microemulsion in comparison to the rats treated with oral microemulsion and nasal solution. Higher concentration of phenytoin was found in rats treated with intranasal microemulsion in comparison to the rats treated with phenytoin solution administered intraperitoneally. Gamma scintigraphy results also suggested faster availability of drug into brain when microemulsion was administered intranasally.