Abstract This contribution reported the equilibrium solubility of aprepitant (form I) in four binary aqueous mixtures of methanol, ethanol, acetone and 1,4-dioxane acquired through a shake-flask method from 283.15 K to 323.15 K under local atmospheric pressure of 101.2 kPa. At the same mass fraction compositions of methanol/ethanol/acetone/1,4-dioxane and temperature, the mole fraction solubility of aprepitant was greater in (1,4-dioxane + water) mixture than in ethanol/acetone/methanol (1) + water (2) mixtures. The relative importance of solute-solvent and solvent-solvent interactions upon the solubility variation was studied by using the linear solvation energy relationships of solvent effect. The Hildebrand solubility parameter and dipolarity-polarizability of the solvents had the main contributions to the solubility variation in methanol/ethanol/1,4-dioxane + water mixtures; while merely dipolarity-polarizability, in (acetone + water) mixture. The preferential solvation was studied by using the method of inverse Kirkwood-Buff integrals in terms of thermodynamic solution properties. The preferential solvation parameters for methanol, ethanol, acetone and 1,4-dioxane presented positive values in methanol/ethanol/acetone/1,4-dioxane-rich and intermediate compositions in the four mixtures, indicating that aprepitant (I) was solvated preferentially by the methanol/ethanol/acetone/1,4-dioxane. It is conjecturable that in these regions aprepitant (I) acts as a Lewis acid with methanol/ethanol/acetone/1,4-dioxane molecules. Moreover, the drug’s solubility was mathematically represented via the Jouyban-Acree model obtaining the average relative deviations less than 6.21%. Finally, the standard dissolution enthalpies ( Δ H sol o ) for aprepitant (I) dissolved in solvent mixtures were obtained from the van’t Hoff analysis.

中文翻译：

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阿瑞匹坦（I 型）在甲醇、乙醇、丙酮和 1,4-二恶烷的四种二元水性混合物中的平衡溶解度测定和热力学方面

摘要 该贡献报告了阿瑞匹坦（I 型）在甲醇、乙醇、丙酮和 1,4-二恶烷的四种二元水性混合物中的平衡溶解度，该混合物通过摇瓶法在 101.2 kPa 当地大气压下从 283.15 K 到 323.15 K 获得. 在甲醇/乙醇/丙酮/1,4-二氧六环的质量分数组成和温度相同的情况下，阿瑞匹坦在（1,4-二氧六环+水）混合物中的摩尔分数溶解度大于乙醇/丙酮/甲醇（1） + 水 (2) 混合物。通过使用溶剂效应的线性溶剂化能关系，研究了溶质-溶剂和溶剂-溶剂相互作用对溶解度变化的相对重要性。Hildebrand 溶解度参数和溶剂的偶极-极化率对甲醇/乙醇/1,4-二恶烷+水混合物中的溶解度变化有主要贡献；而只是偶极极化，在（丙酮+水）混合物中。在热力学溶液性质方面，通过使用逆柯克伍德-布夫积分的方法研究了优先溶剂化。甲醇、乙醇、丙酮和 1,4-二恶烷的优先溶剂化参数在甲醇/乙醇/丙酮/富含 1,4-二恶烷的四种混合物和中间体组合物中呈正值，表明阿瑞匹坦 (I) 优先溶剂化由甲醇/乙醇/丙酮/1,4-二恶烷组成。可以推测，在这些区域中，阿瑞匹坦 (I) 与甲醇/乙醇/丙酮/1,4-二恶烷分子一起充当路易斯酸。而且，药物的溶解度通过 Jouyban-Acree 模型以数学方式表示，获得的平均相对偏差小于 6.21%。最后，从范特霍夫分析中获得溶解在溶剂混合物中的阿瑞匹坦 (I) 的标准溶解焓 (Δ H sol o )。