Correlation of solubility of pioglitazone hydrochloride in different binary solvents

• The solubility of pioglitazone hydrochloride in different binary solvents was investigated.
• The results show that the two models agree well with the experimental data.
• The thermodynamic functions of solution were obtained from these solubility data.
• The dominant mechanisms of solvent action are enthalpy–entropy compensation.

The solubility of pioglitazone hydrochloride (Form I) was measured by the synthetic method in methanol–ethanol, methanol–1-propanol, methanol–acetone mixtures at temperatures ranging from 283.15 K to 323.15 K. The solubility of pioglitazone hydrochloride (Form I) increased with increasing temperature. At a given temperature, solubility in different mixtures follows different rules. The experimental data were effectively correlated by the (CNIBS)/Redlich–Kister model and the modified Apelblat model. The thermodynamic functions (enthalpy, entropy, and molar Gibbs free energy) of solution, mixing and the activity coefficient were then calculated in different solvent mixtures. The dominant mechanisms of the solvent action for pioglitazone hydrochloride (Form I) in different mixtures were analyzed and explained by enthalpy–entropy compensation. The solubility behavior for different mixtures may be controlled by a different mechanism.

Enthalpy–entropy compensation plot for pioglitazone hydrochloride in three mixtures: ■, methanol + ethanol; ●, methanol + 1-propanol; ▴, methanol + acetone.Figure optionsDownload as PowerPoint slide