Experimental Measurement and Correlation of Solubility of Sitagliptin in Twelve Pure Solvents from 278.15 to 323.15 K

The solubility of sitagliptin in the range of 278.15–323.15 K was studied by the gravimetric method. Twelve solvents including water, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, s-butanol, i-pentanol, acetonitrile, tetrahydrofuran, methyl acetate, and ethyl acetate were involved. The experimental results demonstrated a positive temperature dependence of sitagliptin solubility across all investigated solvent systems. The solubility data in 12 pure solvents were systematically correlated using three thermodynamic models: the Yaws equation, the modified Apelblat equation, and the λh equation. Comparative analysis of the average relative deviation and root-mean-square deviation values revealed that the modified Apelblat model provided the most accurate correlation with the experimental data. Furthermore, the solvent effects on sitagliptin solubility were quantitatively analyzed through the Kamlet–Taft linear solvation energy relationship model. These solubility results enable the systematic development and process optimization for sitagliptin crystallization.