Li Xinbao, Cong Yang, Li Wentian, Yan Pengyao, Zhao Hongkun
School of Environmental & Municipal Engineering, North China University of Water Resources and Electric Power, ZhengZhou, He'nan 450011, People's Republic of China.
College of Chemistry & Chemical Engineering, YangZhou University, YangZhou, Jiangsu 225002, People's Republic of China.
J Chem Thermodyn. 2017 Dec;115:74-83. doi: 10.1016/j.jct.2017.07.027. Epub 2017 Jul 24.
The equilibrium solubility of ribavirin in solvent mixtures of {methanol (1) + water (2)}, {-propanol (1) + water (2)}, {acetonitrile (1) + water (2)} and {1,4-dioxane (1) + water (2)} was determined experimentally by using isothermal dissolution equilibrium method within the temperature range from (278.15 to 318.15) K under atmospheric pressure (101.1 kPa). At the same temperature and mass fraction of methanol (-propanol, acetonitrile or 1,4-dioxane), the mole fraction solubility of ribavirin is greater in (methanol + water) than in the other three solvent mixtures. The preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood-Buff integrals. The preferential solvation parameters for methanol, -propanol, acetonitrile or 1,4-dioxane ( ) were negative in the four solvent mixtures with a very wide compositions, which indicated that ribavirin was preferentially solvated by water. Temperature had little effect on the preferential solvation magnitudes. The higher solvation by water could be explained in terms of the higher acidic behaviour of water interacting with the Lewis basic groups of the ribavirin. Besides, the solubility of the drugs was mathematically represented by using the Jouyban-Acree model, van't Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model obtaining average relative deviations lower than 1.57% for correlative studies. It is noteworthy that the solubility data presented in this work contribute to expansion of the physicochemical information about the solubility of drugs in binary solvent mixtures and also allows the thermodynamic analysis of the respective dissolution and specific solvation process.
采用等温溶解平衡法，在常压（101.1 kPa）、温度范围为（278.15至318.15）K的条件下，实验测定了利巴韦林在{甲醇(1)+水(2)}、{正丙醇(1)+水(2)}、{乙腈(1)+水(2)}和{1,4 -二氧六环(1)+水(2)}溶剂混合物中的平衡溶解度。在相同温度和甲醇（正丙醇、乙腈或1,4 -二氧六环）质量分数下，利巴韦林在（甲醇 + 水）中的摩尔分数溶解度大于在其他三种溶剂混合物中的溶解度。通过反柯克伍德 - 布夫积分从其热力学溶液性质推导出优先溶剂化参数。在组成范围很宽的四种溶剂混合物中，甲醇、正丙醇、乙腈或1,4 -二氧六环（ ）的优先溶剂化参数均为负，这表明利巴韦林优先被水溶剂化。温度对优先溶剂化程度影响不大。水的较高溶剂化作用可以用水与利巴韦林的路易斯碱性基团相互作用时更高的酸性行为来解释。此外，用Jouyban - Acree模型、范特霍夫 - Jouyban - Acree模型和阿佩尔布拉特 - Jouyban - Acree模型对药物溶解度进行数学表示，相关研究的平均相对偏差低于1.57%。值得注意的是，本工作中给出的溶解度数据有助于扩展关于药物在二元溶剂混合物中溶解度的物理化学信息，也有助于对各自的溶解和特定溶剂化过程进行热力学分析。
