Solubility Determination, Thermodynamic Analysis, and Molecular Simulation of Anastrozole (I) in Pure and Binary Solvents

The solubility and thermodynamic profile of anastrozole (I) were comprehensively examined across diverse solvent systems through equilibrium gravimetric measurements conducted between 283.15 and 323.15 K under ambient pressure. The measured solubility of anastrozole (I) showed a positive correlation with temperature. Subsequently, the experimental data were correlated using four thermodynamic models, namely, the van’t Hoff, modified Apelblat, RK-4, and λ h models. The results indicated that all models can reproduce the experimental data with high accuracy, among which the Apelblat equation exhibited a superior fitting performance compared with the other models. Then, thermodynamic analysis based on the van’t Hoff and Gibbs equations indicated that the dissolution process of anastrozole (I) is endothermic and enthalpy-driven in all the studied systems. Moreover, FT-IR, PXRD, and TG-DSC analyses indicated that anastrozole (I) possessed a stable structure during the solubility experiments. Furthermore, molecular simulation results supported the experimental observations by indicating that hydrogen bonding and dispersion forces play key roles in solute–solvent interactions. The dissolution behavior was dependent on solvent polarity and the solvation free energy.