Tolnaftate (TNF) is a local antifungal agent.The determination of its solubility can serve as a valuable reference for its crystallization and formulation design, an area that has not yet been comprehensively investigated.In this study, the static method was carried out to determine the solubility of TNF in 10 mono-solvents (methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, n-octanol, 1,2-propanediol, ethylene glycol, acetic acid) and the binary mixed solvents (acetic acid + ethylene glycol) at T = (283.15 to 328.15) K and P = 0.1 MPa.The experiment results showed that TNF dissolves best in acetic acid and worst in ethylene glycol among investigated mono-solvents.And the solubility in mixed solvents was observed to increase as the mole ratio of acetic acid augments.In all solvents, there is obviously increase in the solubility of TNF as temperature elevates.The Apelblat model, van't Hoff model, Jouyban model, GCM model, Sun model and Apelblat-Jouyban-Acree model were used to fit the solubility values.And the root mean square deviation (RMSD) between the calculated values and exptl. values are less than 0.025%, showing that the exptl. values are accurate and the models have good fitting effects.At the same time, X-ray powder diffraction (PXRD) tests confirmed that the absence of crystal transformation during the process of TNF dissolutionIn addition, according to the KAT-LSER model, the influence of solute-solvent interactions on the solubility of TNF exceeds that of solvent-solvent interactions.The thermodn. properties including entropy (ΔH0sol), enthalpy (ΔS0sol), Gibbs free energy (ΔG0sol), enthalpy contribution (%ξH) and entropy contribution (%ξS) were calculated, which proved that dissolution process of TNF is endothermic and entropy-driven, and enthalpy mainly affects Gibbs free energy.
