Chemical enhancement of amorolfine hydrochloride transungual delivery

Abstract

Introduction. Topical therapy of nail diseases is considered highly challenging due to low permeability of the active substances into the nail plate. Chemical penetration enhancers may be used to improve the drug delivery across the nail plate. In the present study, several chemicals were evaluated as transungual delivery enhancers. The aim of the study. To determine the efficacy of various chemicals in improving amorolfine HCl transungual delivery. Materials and methods. Bovine hooves membranes were used as a nail model. For “enhancer only” formulations the predefined concentrations of chemicals in acidified water (pH 3) were produced. Membranes were placed into above formulations and kept at 35°C for 24 hours. After washing and drying, hooves’ membranes were weighed, placed into active substance solutions (500 μg/ml) and incubated for 24 hours at 35°C. Membranes were washed and active substances were extracted and analyzed. The controls were carried out using “drug only” formulation. Thioglycolic acid and urea as potential enhancers were incorporated into 5% amorolfine hydrochloride nail lacquers, containing 96% ethanol as solvent, Eudragit E100 polymer as film-former and Transcutol P as plasticizer. Release of amorolfine hydrochloride was evaluated by applying modified dissolution method. Mean values and standard deviations of the results were calculated. Results. The keratolytic agent salicylic acid increased amorolfine HCl uptake two-fold. It was determined, that nonionic surfactants Tween 60 or Tween 40 decrease the uptake of tested drug. 5%, 10% thioglycolic acid and 5% urea increased amorolfine HCl uptake two fold compared to control. Also it was observed, that 10% thioglycolic acid aggressively etches the surface of membranes, and such concentration should not be recommended for human nails treatment. Biopharmaceutical analysis revealed, that 5% thioglycolic acid increased amorolfine HCl release from nail lacquers two fold, whereas 5%..