FORMULATION AND EVALUATION OF MICROEMULSION BASED IN SITU GEL FOR NASAL DELIVERY OF FLUCONAZOLE
Fluconazole (FLZ) being drug of choice is slightly water soluble (5.1mg/ml) azole efficiently treating fungal infection if available locally in therapeutic dose. In present work intranasal system is developed as a microemulsion based in-situ gel containing 1.5% w/v fluconazole. Cinnamon oil was used as an antifungal oil, surfactants (Tween-80,20) and co-surfactants (PEG-400, IPA, Propylene glycol) was evaluated. After that Construction of Pseudo-Ternary Phase Diagram was done to study the phase behaviour of microemulsion. Pseudo ternary phase diagrams were developed using the aqueous titration method. The microemulsion system was optimized through D-optimal design and an equivalent amount of microemulsion was incorporated in poloxamer 407: poloxamer 188 (2:1) to form a thermosensitive gel. D optimal design was used to optimise the microemulsion based on a pseudoternary phase diagram with three variables: oil(X1), Smix(X2), and water(X3). The results of optimized batch (batch 11) of microemulsions shows 106.2% transmittance, -0.9 mV zeta potential, 208 nm globule size, 0.458 PDI, 28.2 cP viscosity and 99.91% drug content. Also, the optimized batch of microemulsion based in-situ gel shows 34° C gelation temperature with 110 sec as gelling time and having 181cP, 99.1% drug content with 25.5 gm mucoadhesion strength. The in vitro drug release study and ex vivo permeation study shows 95.75% and 85.45% at 4 hours respectively, which initially gives burst release and as it turns into gel release rate decreases. The microemulsion based in-situ gel shows larger zone of inhibition. The microemulsion and microemulsion based in-situ gel were stable at both 4 °C and room temperature.