Synergistic solvation effect and modeling of itraconazole solubility in eight binary mixtures (dichloromethane and chloroform + primary alcohol) at the range of 288.15 K to 308.15 K

Abstract

In this study, the solubility and apparent thermodynamic parameters of itraconazole in chlorinated methane (dichloromethane and chloroform) + primary alcohol (methanol, ethanol, n-propanol, and n-butanol) mixtures were determined at 288.15–308.15 K utilizing the well-established shake-flask technique. The experimental mole fraction solubility of itraconazole in all studied binary solvent mixtures gradually increased as the temperature rises. Because of the synergy effect between chlorinated methane and primary alcohol mixtures, the solubility of itraconazole was maximal in chlorinated methane + primary alcohol mixtures with a 0.9 mass fraction of chlorinated methane at all tested temperatures. The solubility profile of itraconazole in chlorinated methane + primary alcohol mixtures can be explained by the synergistic effect and solubility parameters. Additionally, thermal and crystal analyses confirmed that no polymorphic transformation occurred during the dissolution processes of itraconazole. The experimental solubility of itraconazole in chlorinated methane + primary alcohol mixtures were adequately fitted and correlated with eight well-known correlation models. The modified van’t Hoff and Gibbs equations were applied to better understand and calculate the thermodynamics of itraconazole dissolved in chlorinated methane + primary alcohol mixtures. The experimental solubility and calculated solubility of itraconazole in eight binary mixtures can be helpful for drug development, such as pre-formulation study, separation, crystallization, extraction, purification, and solubilized drug formulation.