Abstract

Systemic administration of voriconazole, a novel anti-fungal agent, is associated with adverse effects including visual disturbances and hepatic abnormalities. The purpose of this study was to improve the aqueous solubility of voriconazole using 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and to study the effect of addition of viscosity modifiers to these solutions. Statistical analysis was done by one-way analysis of variance followed by Dunnett's test. The phase solubility studies indicated that voriconazole solubility increased with increase in HP-β-CD concentration. Using a combination of chitosan 0.2%, BAK 0.01% and EDTA 0.01% in voriconazole- HP-β-CD based aqueous drops (1.5%, pH 7.0), a 3.9 times and 5.4 times higher Papp was obtained than with formulation without chitosan and control formulation (without chitosan and preservative), respectively. Thus, it could be concluded voriconazole aqueous drops formulated using HP-β-CD can be used topically for the treatment of fungal keratitis and the addition of chitosan to the voriconazole aqueous drops can produce significantly higher permeation.

Keywords: Chitosan, Fungal keratitis, HP-β-CD, Phase solubility, Transcorneal permeation, Voriconazole.