Ointment for Topical Ocular Delivery of Voriconazole: Formulation Development, In-Vitro Characterization & In-Vivo Pharmacokinetic Assessment.

Abstract

Voriconazole (VCZ) is a broad-spectrum antifungal agent widely used for treating fungal infections caused by Candida, Aspergillus, and Fusarium species, which are commonly associated with fungal keratitis (FK). Topical ophthalmic ointments offer several advantages over conventional eye drops, including prolonged retention on the ocular surface, sustained drug release, and improved bioavailability. In this study, we formulated and optimized a VCZ-loaded ophthalmic ointment intended for effective management of FK. The ointments were prepared using emulsifying wax and varying proportions of liquid paraffins through the fusion method. Among all the formulations, batch F4 demonstrated optimal properties, including a stable, opaque white appearance with drug content of 103.7 ± 2.4%. Microscopic examination showed no drug crystallization, and differential scanning calorimetry (DSC) confirmed the absence of drug-excipient interactions. The in vitro release profile of F4 showed 70% drug release over 24 h, fitting the Higuchi kinetic model, indicative of a sustained release pattern. Ex vivo transcorneal studies revealed that 13.22 ± 0.81% of the drug permeated across the cornea, while 2.51 ± 0.03% remained entrapped in the corneal tissue after 24 h. Ocular irritation studies demonstrated the formulation was non-irritant and safe for ophthalmic use. Furthermore, in vivo pharmacokinetic evaluation in rabbits showed significantly higher corneal drug concentrations for F4 (C_max: 400.76 ± 70.13 μg/mL) compared to a marketed formulation (C_max: 32.60 ± 26.64 μg/mL), indicating approximately 12-fold enhanced retention. These findings suggest that the optimized ointment is a promising option for effective and prolonged ocular delivery of VCZ in the treatment of FK.