Solubility determination, hansen solubility parameter, solvent effect and preferential solvation of thenalidine in four aqueous binary mixtures

The equilibrium solubility of thenalidine in four solvent mixtures (ethanol + water, n -propanol + water, isopropanol + water, and N,N -dimethylformamide (DMF) + water) was studied using the isothermal saturation method at temperatures ranging from 278.15 to 323.15 K under 101.2 kPa. For the mixed systems, the increase in temperature was positively correlated with an increase in solute dissolution. Besides, the water content in the solvent was also a variable that cannot be ignored in the dissolution results. The solubility data in mixed solvents were correlated and calculated by Jouyban-Acree model (J-A), van’t Hoff-Jouyban-Acree model (V-J-A) and Modified Apelblat-Jouyban-Acree model (A-J-A). The largest values of the relative average deviation ( RAD ) and the root-mean-square deviation ( RMSD ) were 4.75 × 10 −2 and 0.79 × 10 −4 , respectively. These values were obtained upon using n -propanol + water and DMF + water, respectively. The Hansen solubility parameter was effective for exploring the dissolution behavior of thenalidine in different solvents considering the interaction between solvent and solute molecules. Furthermore, the solvent effect related to thenalidine dissolution was evaluated through the KAT-LSER model, which indicated that the solute–solvent molecule interactions were critical. Finally, the derivation of the preferential solvation parameters ( δx 1,3 ) of thenalidine was achieved by the method of inverse Kirkwood–Buff integrals. For ethanol/ n -propanol/isopropanol + water, the thenalidine was preferentially dissolved in ethanol/ n -propanol/isopropanol within intervals of 1 >  x 1  > 0.24, 1 >  x 1  > 0.19 and 1 >  x 1  > 0.13, respectively. In contrast, thenalidine dissolved preferentially in water in other intervals. However, for DMF + water, | δx 1,3 | was less than 1 × 10 −2 , thus, the preferential solvation theory was not applicable for this system.