Corneal targeted Amorolfine HCl-mixed micelles for the management of ocular candidiasis: Preparation, in vitro characterization, ex vivo and in vivo assessments

Amorolfine Hydrochloride (AMO) is a broad-spectrum antifungal drug commonly used to treat onychomycosis. This work aims to introduce AMO as a new alternative for the management of oculomycosis, where its delivery to the corneal tissue is hindered by the poor aqueous solubility, besides further obstacles fronting the ophthalmic delivery such as brief residence time, and the prevailing anatomical barrier. This work presents the formulation of AMO-mixed micelles (AMO-MMs) incorporating Solutol HS15 and Pluronic F127 as surfactants and propylene glycol (PG) as a co-surfactant. The mixed micelles were prepared by the thin film hydration method and planned on the basis of a 32 21 factorial design. The optimal formulation F5 (Desirability = 0.788) was prepared with 5% total surfactants (SAA), Solutol HS15: Pluronic F127 1:1 ratio, and 0.5% PG. The particle size, the zeta potential value, and the drug loading percentage were 26.55 +/- 1.68 nm, -2.90 +/- 0.41 mV, and 7.49 +/- 0.01%, respectively. The solid-state characterization results confirmed the dispersion of the drug in the mixed micelles. The ex vivo permeation study was performed on cow cornea using labeled MMCs with a fluorescent dye to test corneal penetrability of the optimal formulation through confocal laser scanning microscopy. The minimum inhibitory concentration (MIC) of the optimal formulation was compared to the standard market product; Natamycin (5%) ophthalmic suspension, against the Candida albicans strain using the microdilution method which was 3 folds less than that of the standard market product. Furthermore, the safety and efficacy profiles of the optimal formulation were studied and compared to the standard market product via an in vivo study on male Albino rabbits, which proved the biosafety and effectiveness of the optimal formulation. Inclusively, AMO-MMs could be an auspicious corneal delivery system for the management of fungal keratitis.