Investigation on Dissolution of S-Ketoprofen in Aqueous Mixtures: Solubility Measurement and Model Correlation, Co-Solvency, Solvent Effect, and Preferential Solvation

The solubility remains critical in drugs development, manufacturing, and application. S-Ketoprofen (SKTP) solubility in methanol/ethanol/2-propanol/acetone + water (278.15–318.15 K) was measured by the isothermal saturation technique. The impacts of solvent effect, Hansen solubility parameters (HSPs), and preferential solvation on solubility and model correlation were analyzed. The SKTP solubility increased with decreasing water content in alcohols–water but exhibited cosolvency at w = 0.80 in acetone–water; the maximum mole fraction solubility is 0.1072. The HSPs explained the occurrence of cosolvency molecularly (minimum Δδ_t = 0.08 at w = 0.80, acetone composition). The solvent effect analysis showed that solute–solvent or solvent–solvent interactions account for 63.44 and 32.60% of solvent effect. Thus, hydrogen bonding and nonspecific dipolarity/polarizability interactions dominate SKTP dissolution. The preferential solvation investigation indicated that SKTP was preferentially dissolved by cosolvents within 0.32 < x₁ < 1 for methanol–water, 0.23 < x₁ < 1 for ethanol–water, 0.17 < x₁ < 1 for 2-propanol–water, and 0.21 < x₁ < 0.55 for acetone–water but preferentially dissolved by water in other region. The correlation results suggested that the maximum values of relative average deviation and root-mean-square deviation were 4.84% and 9.45 × 10^–4, thus Apelbat–Jouyban–Acree, Jouyban–Acree, and van’t Hoff–Jouyban–Acree models can correlate the solubility data accurately.