Solubility Measurement and Correlation of Itraconazole Hydroxy Isobutyltriazolone in Four Kinds of Binary Solvent Mixtures with Temperature from 283.15 to 323.15 K.

ABSTRACT

The solubility of itraconazole hydroxy isobutyltriazolone (IHI) in four commonly used binary solvent mixtures of N,N-dimethylformamide (DMF) + water, DMF + ethanol, tetrahydrofuran (THF) + water, and THF + ethanol was determined with gravimetric method at temperatures ranging from 283.15 to 323.15 K under atmospheric pressure. The solubility of IHI in all selected solvents increases with the increase of temperature. The maximum solubility of IHI exists in the solvent of DMF + ethanol (0.06523 mol·mol-1, x20 = 0.7, T = 323.15 K), while the minimum solubility exists in DMF + water (0.0003723 mol·mol-1, x20 = 0.3, T = 283.15 K). There is a co-solvency phenomenon in the mixed solvents of DMF+ ethanol, THF + water, and THF + ethanol. Four thermodynamic models, including the modified Apelblat model, the Yaws model, the Sun model, and the modified Jouyban-Acree model, were selected to fit the solubility data of IHI. All the RAD values are less than 0.0484, and RMSD values are not more than 0.001319. The Yaws model and the modified Apelblat model fit the solubility data of IHI better than the other two models. All the selected four models can fit the solubility data of IHI well.