Abstract In this research work, laser monitoring method was employed to investigate the mole-fraction solubility data of α adrenergic receptor agonists (R)-(-)-phenylephrine hydrochloride (R-PEHC) in three binary solvents namely “methanol (MtOH) + ethanol (EtOH), MtOH + isopropanol (IPOH) and EtOH + IPOH” over the temperature of (278.15 - 323.15) K with temperature range of 5 K under 0.1 MPa. The results demonstrated that experimental solubility was positively related with temperature while inversely associated with mass fraction of anti-solvents. At the same temperature and mass fraction of anti-solvent, the general solubility order of R-PEHC in binary solvents was MtOH + EtOH > MtOH + IPOH > EtOH + IPOH. Meanwhile, Hansen solubility parameter (HSP) was employed to investigate the solubility order, and the results showed solubility behavior could be analyzed well by selected four solubility parameters (Δδp, Δδh, Δδt and Δδ). Besides, the molecular simulation technology was conducted to investigate solvation free energy (Esol) between R-PEHC and selected solvents. The results showed that experimental solubility differences in various solvents were attributed to the differences in solvation free energy. Moreover, mathcad software (Version: 15) was applied to correlate experimental solubility with respect of temperatures by using five thermodynamic models (UNIQUAC, Wilson, Three-Suffix Margules, Jouyban-Acree-modified Apelblat (J-A-A) and NRTL model). All selected models provided satisfactory goodness-of-fit with R-PEHC solubility data. Furthermore, apparent thermodynamic properties of solutions were calculated based on van’t Hoff equation as well as experimental solubility, the results indicated that dissolution process was always endothermic and entropy-driven.

中文翻译：

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(R)-(-)-苯肾上腺素盐酸盐在三种二元溶剂中的溶解度测量、模型评估和分子模拟

摘要 本研究采用激光监测方法研究了α肾上腺素能受体激动剂(R)-(-)-苯肾上腺素盐酸盐(R-PEHC)在“甲醇(MtOH)+”三种二元溶剂中的摩尔分数溶解度数据。乙醇 (EtOH)、MtOH + 异丙醇 (IPOH) 和 EtOH + IPOH”，温度为 (278.15 - 323.15) K，温度范围为 5 K，0.1 MPa。结果表明，实验溶解度与温度呈正相关，与反溶剂的质量分数呈负相关。在相同温度和反溶剂质量分数下，R-PEHC在二元溶剂中的一般溶解度顺序为MtOH+EtOH>MtOH+IPOH>EtOH+IPOH。同时，采用汉森溶解度参数（HSP）来研究溶解度顺序，结果表明，选择四个溶解度参数（Δδp、Δδh、Δδt和Δδ）可以很好地分析溶解度行为。此外，还进行了分子模拟技术以研究 R-PEHC 与选定溶剂之间的溶剂化自由能 (Esol)。结果表明，实验在各种溶剂中的溶解度差异归因于溶剂化自由能的差异。此外，通过使用五种热力学模型（UNIQUAC、Wilson、三后缀 Margules、Jouyban-Acree-modified Apelblat (JAA) 和 NRTL 模型），应用 mathcad 软件（版本：15）将实验溶解度与温度相关联。所有选定的模型都提供了令人满意的 R-PEHC 溶解度数据拟合优度。此外，