KETOCONAZOLE LADEN MICROEMULSION BASED GEL FORMULATION AGAINST SKIN FUNGAL INFECTION

Abstract

Objective: The present research was aimed to develop ketoconazole (KT) loaded microemulsion-based gel formulation for effective topical delivery through enhanced drug solubility, improved skin permeation and reduced side effects overcoming drawbacks of conventional dosage forms. Methods: For the selection of oil, surfactant and co-surfactant mixture (Smix) ratio, the phase titration method was used and pseudo-ternary phase diagrams were prepared. D-optimal mixture design was employed to optimize the microemulsion system taking oil, Smix and water as independent variables and particle size, polydispersity index, zeta potential, % transmittance and cumulative % drug release as response variables. Finally, topical gel formulation of KT-loaded microemulsion was developed and evaluated for physico-chemical properties, rheological properties, in vitro drug release kinetics and ex-vivo drug permeation. Results: The optimized microemulsion was found to be a transparent formulation with 19.7 nm particle size, 0.268 polydispersity index,-0.2 mV zeta potential, 97.83% transmittance and 85.85% cumulative drug release at 24 h. The developed gel of optimized microemulsion possessed pH 6.20, viscosity 2178 cps, spreadability 18.634 g.cm2/sec, adhesiveness 45.989 N/mm2, and cohesiveness-85.583. The in vitro drug release was found to be 69.08 % (at 24 h), showing sustained release and Higuchi kinetic profile. The developed gel exhibited 1.84-fold higher drug permeation flux as compared to the marketed product. Conclusion: The developed gel formulation possessed all desired quality attributes and physico-chemical properties. The in vitro and ex-vivo study data proved it’s suitability as a better alternative to conventional products in the effective treatment of fungal skin infections.