Bezafibrate in several aqueous mixtures of low alcohols: Solubility, solvent effect and preferential solvation

By using the saturation shake-flask method, the saturated solubility of bezafibrate in neat water, methanol, ethanol, n-propanol and isopropanol and aqueous co-solvent mixtures of methanol (1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and n-propanol (1) + water (2) was experimentally acquired at temperatures from 283.15 Kto 323.15 K and local atmospheric pressure. The maximum solubility magnitudes in mole fraction were recorded in the neat solvents of methanol/ethanol/n-propanol/ isopropanol for corresponding solutions. The mole fraction solubility was described mathematically by using the van't Hoff-Jouyban-Acree and Jouyban-Acree models. The largest value of relative average deviations was 6.23%; and, root-mean-square deviations, 8.92 x 10(5). The local mole fractions of water and co-solvent (methanol, ethanol, n-propanol or isopropanol) around the drug bezafibrate were quantitatively investigated by the use of Inverse Kirkwood-Buff integrals method. Results indicated that the bezafibrate was preferentially solvated by methanol (ethanol, n-propanol or isopropanol) in alcoholrich and intermediate compositions in the alcohol mixtures; while in water-rich compositions, bezafibrate was preferentially solvated by water. The main factors relating to solvent effect were inspected through Kamlet and Taft linear solvation energy relationships, demonstrating that the cavity formation energy and dipolarity-polarizability in methanol solutions, cavity formation energy and basicity in ethanol solutions, and cavity formation energy in n-propanol (isopropanol) solutions played the principal role upon the bezafibrate solubility variation. (C) 2020 Published by Elsevier Ltd.

Automated summary

The study experimentally investigated the saturated solubility of bezafibrate in various solvents and aqueous co-solvent mixtures, and mathematically described the mole fraction solubility using different models. The preferential solvation of bezafibrate by different solvents in alcohol-rich and water-rich compositions was quantitatively analyzed. The main factors related to solvent effect were identified through linear solvation energy relationships.