The solubilities of fluoxetine hydrochloride (FH) in pure solvents including methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, s-butanol, n-pentanol, i-pentanol, acetone, 2-butanone, cyclohexanone, acetonitrile, tetrahydrofuran, and chloroform and binary solvent mixtures (methanol + water) were determined by a static gravimetric method at temperatures ranging from 278.15 to 318.15 K under atmospheric pressure. Thermodynamic models including the modified Apelblat model, λh model, NRTL model, and Wilson model were chosen to fit the solubility data in neat solvents, and the CNIBS/R-K model, modified Jouyban−Acree model, NRTL model, and Wilson model were selected to correct the solubility data of FH in binary solvent mixtures. The NRTL model fitted the experimental data best among all the selected models in pure solvents, with RAD = 0.0013, rmsd = 0.000022, and the CNIBS/R-K model fitted best in the binary solvent mixtures of methanol + water (with RAD = 0.0133, rmsd = 0.000349). Finally, the dissolution properties (i.e., the dissolution enthalpy, entropy, and Gibbs energy changes) of FH were calculated based on the Wilson model. The experimental data for FH will provide significant guidance for optimization of the crystallization process.
