Self-nanoemulsifying drug delivery system to improve transcorneal permeability of voriconazole: in-vivo studies

Abstract

Objective This study investigates the effectiveness of self‐nanoemulsifying drug delivery system (SNEDDS) in improving voriconazole transcorneal permeability. Methods Voriconazole‐SNEDDS was prepared with isopropyl myristate, PEG 400, Tween 80^® and Span 80^® and was subjected for physicochemical characterization after reconstitution with NaCl 0.9% (1/9; v/v). In‐vitro antifungal activity was assessed and compared with the marketed formulation. In‐vivo studies, namely ocular irritation test via modified Draize test and pharmacokinetic study, were investigated using rabbit as animal model. Key findings Voriconazole‐SNEDDS presented a droplet size of 21.353 ± 0.065 nm, a polydispersity index of 0.123 ± 0.003, a pH of 7.205 ± 0.006 and an osmolarity of 342.667 ± 2.517 mOsmol/l after reconstitution with NaCl 0.9%. Voriconazole‐SNEDDS minimum inhibitory concentration (MIC₉₀) was similar to the one of marketed formulation for Candida species while it was significantly lower (P < 0.001) for Aspergillus fumigatus. Draize test revealed that Voriconazole‐SNEDDS was safe for ocular administration. Voriconazole maximum concentration (5.577 ± 0.852 µg/ml) from SNEDDS was higher than marketed formulation (C_max = 4.307 ± 0.623 µg/ml), and the T_max was delayed to 2 h. The area under the concentration–time curve value of Voriconazole‐SNEDDS was improved by 2.419‐fold. Conclusion Our results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery and this encourages further clinical studies.