Application of central composite design for the optimization of itraconazole loaded nail lacquer formulation.

Abstract

Onychomycosis is a common fungal infection of the nails that mostly affects the elderly and athletes. Antifungal drug-like itraconazole is one of the therapeutic agents of choice for the topical treatment of onychomycosis. The current work aimed for the preparation and optimization of itraconazole-loaded nail lacquer formulation. Central composite design was employed; independent variables were polymer concentration (X1) and thioglycolic acid (TGA) concentration (X2). While the dependent variables were cumulative amount of drug permeated per unit area (CADP/A, Y1), drying time (Y2) and nonvolatile content (Y3). The optimized formulation was characterized for various parameters including ex-vivo permeation study, confocal laser scanning microscopy (CLSM) and antifungal study. The optimized nail lacquer formulation (F7) exhibited CADP/A of 198.23µg/cm2, drying time of 185s and nonvolatile content of 97.23%. The scanning electron microscopy of goat hoof treated with optimized nail lacquer formulation demonstrated loosening of the structure and marked increase in surface roughness. The CLSM micrograph of goat hoof treated with optimized nail lacquer formulation demonstrated that the probe dye was eventually distributed and penetrated through the hoof. Bio-adhesiveness analysis showed that the prepared nail lacquer film has ample adhesiveness to be maintained on the nail plate surface for a sufficient time. In antifungal study, the optimized nail lacquer, and marketed gel exhibited a zone inhibition of 21mm, and 10mm against Candida albicans, respectively. The stability study showed that the optimized nail lacquer is stable at storage condition. The prepared nail lacquers have been shown to serve as a useful dosage form for the delivery of itraconazole across nail plate for controlling the problems associated with onychomycosis.