Solubility Modeling, Solvent Effect, and Preferential Solvation of Thiamphenicol in Cosolvent Mixtures of Methanol, Ethanol, N,N-Dimethylformamide, and 1,4-Dioxane with Water

The thiamphenicol solubility in aqueous cosolvent solutions of ethanol (1), methanol (1), 1,4-dioxane (1), and N,N-dimethylformamide (DMF, 1) was measured via the isothermal dissolution equilibrium method at temperatures ranging from 278.15 to 318.15 K under local pressure (101.1 kPa). At fixed composition of ethanol (methanol, 1,4-dioxane, or DMF) and temperature, the solubility of thiamphenicol was larger in DMF + water mixtures than in the ethanol/methanol/1,4-dioxane mixtures. The local solvent proportions were acquired with the method of inverse Kirkwood-Buff integrals. The absolute value of these preferential solvation parameters were all lower than 1.0 X 10(-2) for ethanol (1) + water (2) and 1,4-dioxane (1) + water (2) solutions in water-rich compositions and for methanol (1) + water (2) solutions in whole compositions. In the former two cosolvent mixtures in intermediate compositions and cosolvent-rich regions, thiamphenicol was preferentially solvated by cosolvent. However, for the DMF (1) + water (2) solutions, water solvated preferentially thiamphenicol in water-rich compositions and by DMF in intermediate and DMF-rich compositions. This case by cosolvent might be illustrated based on higher basic behavior of water, which interacted with Lewis acidic groups of thiamphenicol. In addition, the solubility of thiamphenicol was described with the van't Hoff-Jouyban-Acree, Jouyban-Acree, and Apelblat-Jouyban-Acree models. The obtained average relative deviations were no greater than 1.85%. Furthermore, the solvent effect treatment through the KAT-LSER model indicated that the solubility variation was significantly affected by the cavity term.