The utility of thermal analysis in the preformulation and development of an antifungal nail lacquer containing thymol

Abstract

Thymol (TML) is a potent antifungal in which its low aqueous solubility and high volatility limit pharmaceutical exploitation. The study aimed to develop, with the support of thermal analysis, a TML nail antifungal lacquer. For this, preformulation studies were conducted with the different components of the lacquer formulation in binary mixtures. Then, development studies were performed based on a simplex centroid mixture design using Eudragit E (EudE) as a lacquer base, and the excipients hydroxypropyl-β-cyclodextrin (HPβCD), citric acid (CA) and glycerin (GLY). The formulations were characterized regarding their physicochemical properties, drug release profile, stability, and antifungal effect. Thermal studies have demonstrated chemical compatibility between lacquer components and a high stabilization capacity of TML by EudE. The lacquers met the performance requirements for homogeneous film formation and proper drying time (55–80 s) and also were able to control the drug release according to Hixson–Crowell or Higuchi kinetics. As hypostatized, the formulation composition influenced the functional properties of the lacquer. In fact, formulations containing a mixture of all the stabilizing agents in similar proportions (formulation F7) or formulations containing higher ratios of CA together with GLY and HPβCD lead to more favorable results such as higher antifungal effect (up to 240% higher than free TML), better stability (over 95% of TML stabilization under simulated use conditions) and easy removal (almost 90% of lacquer removal in water after 24 h of application).