Transungual Gel of Terbinafine Hydrochloride for the Management of Onychomycosis: Formulation, Optimization, and Evaluation

The present study was aimed to optimize, develop, and evaluate microemulsion and microemulsion-based gel as a vehicle for transungual drug delivery of terbinafine hydrochloride for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the composition of microemulsion having amount of oil (X1), Smix (mixture of surfactant and cosurfactant; X2), and water (X3) as the independent variables. The formulations were assessed for permeation (micrograms per square centimeter per hour; Y1), particle size (nanometer; Y2), and solubility of the drug in the formulation (milligrams per milliliter; Y3). The microemulsion containing 3.05% oil, 24.98% Smix, and 71.96% water was selected as the optimized formulation. The microemulsion-based gel showed better penetration (∼5 folds) as well as more retention (∼9 fold) in the animal hoof as compared to the commercial cream. The techniques used to screen penetration enhancers (hydration enhancement factor, ATR-FTIR, SEM, and DSC) revealed the synergistic effect of combination of urea and n-acetyl cysteine in disruption of the structure of hoof and hence, leading to enhanced penetration of drug.