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 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 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 better alternative to conventional products in effective treatment of skin fungal infections
