Abstract Solubilities of fluphenazine decanoate (FD) in binary mixtures of propylene glycol + water (PG + W) at 293.2, 298.2, 303.2, 308.2, and 313.2 K are reported. The combination of Jouyban–Acree model and van’t Hoff equation is used to predict the solubility of FD in a given solvent mixture at different temperatures. The thermodynamic properties (enthalpy, entropy and Gibbs energy standard changes of solutions) for FD in PG + W mixtures are calculated from solubility data using the modified version of van’t Hoff and Gibbs equations. The results show that Jouyban–Acree model can predict the solubility of FD in PG + W mixtures as a function of temperature over the studied temperature range. The study represents the first time that thermodynamic properties of solutes dissolved in binary solvent mixtures have been described by the Jouyban–Acree model. The calculated values are in good agreement with the measured experimental data.