Abstract 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, 8.92×10-5. 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 alcohol-rich 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.

中文翻译：

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苯扎贝特在几种低级醇的水性混合物中：溶解度、溶剂效应和优先溶剂化

摘要 采用饱和摇瓶法测定苯扎贝特在纯水、甲醇、乙醇、正丙醇和异丙醇以及甲醇（1）+水（2）、乙醇（1）+共溶剂水溶液中的饱和溶解度。水 (2)、异丙醇 (1) + 水 (2) 和正丙醇 (1) + 水 (2) 是在 283.15 K 至 323.15 K 的温度和当地大气压下通过实验获得的。对于相应的溶液，在甲醇/乙醇/正丙醇/异丙醇的纯溶剂中记录以摩尔分数计的最大溶解度大小。摩尔分数溶解度通过使用 van't Hoff-Jouyban-Acree 和 Jouyban-Acree 模型进行数学描述。相对平均偏差的最大值为 6.23%；和，均方根偏差，8.92×10-5。水和共溶剂（甲醇、乙醇、通过使用逆柯克伍德-布夫积分方法对药物苯扎贝特周围的正丙醇或异丙醇进行定量研究。结果表明苯扎贝特优先被甲醇（乙醇、正丙醇或异丙醇）溶解在醇混合物中的富含醇和中间体组合物中；而在富含水的组合物中，苯扎贝特优先被水溶解。通过Kamlet和Taft线性溶剂化能关系考察了与溶剂效应有关的主要因素，表明甲醇溶液中的空穴形成能和偶极极化率、乙醇溶液中的空穴形成能和碱度以及正丙醇中的空穴形成能（异丙醇）溶液对苯扎贝特溶解度变化起主要作用。