Determination and correlation of solubility of efinaconazole in fifteen mono solvents and three binary mixed solvents at various temperatures

Abstract In this study, the solubility data of the solid–liquid equilibrium of efinaconazole in acetone, acetonitrile, 1-butanol, diethylene glycol monoethyl ether (DEGME), dichloromethane, dimethylformamide (DMF), ethanol, ethyl acetate, methanol, 1-propanol, 2-propanol, propylene glycol, polyethylene glycol 400 (PEG 400), tetrahydrofuran, water, and three binary mixed solvents (DEGME + water, ethanol + water, and PEG 400 + water) were measured at five different temperatures (288.15–308.15 K) using the shake-flask technique. The solubility of efinaconazole in the fifteen mono solvents was highest in dichloromethane, followed by tetrahydrofuran, DMF, and acetone, and lowest in water. In the binary mixtures, the solubility of efinaconazole increased with an increase in the DEGME, ethanol, and PEG 400 mass fraction at a defined temperature, respectively. According to the Kamlet-Taft linear solvation energy relationship model analysis, the self-cohesiveness of the solvent indicating solvent–solvent interaction was the main factor affecting the solubility of efinaconazole, which resulted in decreased solubility. Nine models, including the van’t Hoff, modified Apelblat, Buchowski-Ksiazczak λh, simplified CNIBS/R-K, Jouyban-Acree, Jouyban-Acree-van’t Hoff, Jouyban-Acree-modified Apelblat, Sun, and Ma models, were used to regress the experimental solubility data of efinaconazole in fifteen mono solvents and the three binary mixtures. In addition, the dissolution thermodynamic properties of efinaconazole were estimated using a modified van’t Hoff analysis. The experimental solubility data and correlated models of efinaconazole in fifteen mono solvents and the three binary mixed solvents could be useful for the crystallization, purification, and development of liquid dosage forms such as topical solutions during drug development.