Solubility determination of raloxifene hydrochloride in ten pure solvents at various temperatures: Thermodynamics-based analysis and solute-solvent interactions.

The purpose of the present study was to determine the solubility of raloxifene hydrochloride (RHCl) in ten solvents: water, ethanol, isopropyl alcohol (IPA), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), Transcutol, 1-butanol, dimethyl sulfoxide (DMSO), and ethyl acetate (EA) at temperatures of 298.2-323.2 K and a pressure of 0.1 MPa. The solubility data obtained was fitted upon "Apelblat and Van't Hoff" equations. The maximum mole fraction solubility of RHCl was obtained in DMSO (5.02 × 10-2 at 323.2 K), followed by PEG-400 (5.92 × 10-3 at 323.2 K), EA (3.11 × 10-3 at 323.2 K), Transcutol (1.22 × 10-3 at 323.2 K), PG (2.19 × 10-4 at 323.2 K), 1-butanol (1.96 × 10-4 at 323.2 K), IPA (1.47 × 10-4 at 323.2 K), ethanol (7.90 × 10-5 at 323.2 K), EG (6.65 × 10-5 at 323.2 K), and water (3.60 × 10-5 at 323.2 K). Similar fashions were noticed at each studied temperature. The higher solubility of RHCl in DMSO, PEG-400, EA, and Transcutol was possibly referable to their lower polarity in comparison with water. The molecular interactions between the solute and solvent molecules were estimated by calculating parameters like activity coefficients, and more prominent solute-solvent molecular interactions were noted for RHCl-DMSO, RHCl-EA, and RHCl-PEG-400 in comparison with the other solute-solvent combinations. The outcomes of the "apparent thermodynamic analysis" showed that the dissolution of RHCl was "endothermic, spontaneous and entropy-driven" in all investigated solvents. The obtained solubility data of RHCl in commonly used solvents could be useful in the purification, recrystallization, and dosage form design of the drug.