Formulation Development and Optimaztion of Opthalmic Niosomal In-Situ Gel of Voriconazole for Treatment of Fungal Keratitis

Abstract

The aim of the present work is to formulate, develop and optimize the niosomal in-situ gel of Voriconazole for treatment of fungal keratitis. Conventional liquid ophthalmic formulations are most convenient from patient point of view but it shows low bioavability because of constant lachrymal drainage in the eye which leads to frequent dosing. To overcome this limitation different approaches has been applied such as ointment, gel etc. but this also fail to show desired therapeutic response, so two different systems were combined together as niosome and in-situ gel by incorporating niosome in in-situ gel formulation so that it is easy to administered and retain at the site for prolonged period of time. Voriconazole, a broad-spectrum, triazole, anti-fungal drug, which is used in treatment of eye allergic conditions, keratitis, after eye surgery, post cataract treatment. Voriconazole niosomes were prepared by two method solvent injection & thin film hydration by using span 20 as non-ionic surfactant in both processes. Solvent injection method was selected for further optimization because of short process duration, easy recovery, unilamellar vesicle, better entrapment efficiency, desired particle size etc. Effect of various parameters such as surfactant-lipid ratio, and various process parameters were checked and optimized. Box behnkan design was applied for the optimization of final formulation by considering concentration of surfactant, concentration of cholesterol, and sonication time as independent variables. The optimized batch showed desired vesicular size, % entrapment efficiency, and zeta potential value. The prepared niosomes were incorporated into carbopol 934P & HPMC K4M solution, and the prepared niosomal-gel was evaluated for pH, viscosity, appearance, % drug diffusion, % drug retention. Ocular irritancy study and in vivo pharmacokinetic study were performed after administering the formulation into the rabbit eye. Niosomal in-situ gel is viable alternative for conventional eye drops by virtue of its ability to enhance bioavability through its longer residence time and ability to sustain drug retention.