Development and Evaluation of Luliconazole Nail Lacquer Containing Potential Permeation Enhancers for an Enhanced Transungual Drug Delivery

Abstract

Topical therapy for nail infection has a serious drawback of drug permeation via keratinized human nail plate. Onychomycosis, or tinea unguium, is a human nail fungal infection affecting nearly 19% of the world’s population. Purposely, we aimed to develop and evaluate nail lacquer formulations incorporated with luliconazole utilizing different permeation enhancers for targeted transungual drug delivery. Nail clippings were treated with luliconazole solution (5% w/v) with or without permeation enhancers and screened by determining the hydration enhancement factor and retention of the drug in the nail clippings. Different batches of nail lacquer formulations were prepared to employ Eudragit, polyethylene glycol 400, Tween 80, and permeation enhancer with the highest hydration enhancement factor value. Successively, the formulations were evaluated for studies like compatibility, application, gloss, blush, smoothness of flow, adhesion, non-volatile content, etc. Based on the results of physical characterization and in vitro release study, formulations based on Eudragit RLPO and RSPO containing N-acetylcysteine and urea and the Eudragit RL100 containing urea as penetration enhancer were found to be potentially useful. Furthermore, a comparative ex vivo evaluation of the formulations for permeation across the nail clippings revealed that the luliconazole-loaded Eudragit RLPO formulations containing N-acetylcysteine and urea provided the highest flux (5.12 µg/cm2/min) and shortest lag time (17.4 min). Morphological analysis showed an increase in the number of pores on the nail surface, leading to the enhancement of drug diffusion across the nail matrix and nail bed. Furthermore, the luliconazole nail lacquer formulation exhibited higher antifungal activity, viscosity, and stability properties. Hence, the results suggest that the developed luliconazole nail lacquer formulation is an efficient topical transungual drug delivery system.