Artemisinin has been widely used in various countries around the world for the treatment of malaria, which has saved so many lives that it continues to attract the attention of scientific researchers. However, its clinical efficacy and potential applications in other fields could be affected by its poor water-solubility. Thus, it is necessary to study the solubility and crystallization of artemisinin. At the present study, the solubility of artemisinin (Form Ⅰ) in three (tetrahydrofuran + isopropanol, 1,4-dioxane + isopropanol, 1,4-dioxane + n-propanol) binary solvents were measured from 283.15 K to 323.15 K by a gravimetric method. The Ma model, Ideal model, Jouyban-van′t Hoff model and GSM model were selected to fit the obtained solubility. Furthermore, ARD, RMSD and RD were used to evaluate the correlate reliability of the thermodynamic models. The average 100ARD and 10⁴RMSD of the four models were 2.19 (Ma), 1.48 (GSM), 2.18 (Jouyban-van′t Hoff), 1.53 (Ideal) and 12.37 (Ma), 8.27 (GSM), 11.18 (Jouyban-van′t Hoff), 5.74 (Ideal), respectively. Additionally, DSC, TGA, PXRD and crystal morphology characterization analysis were used to analyze the crystal polymorphic change during the artemisinin dissolution process. Besides, Hansen solubility parameters and thermodynamic properties including Δ_solH°, Δ_solS°, Δ_solG°, ζ_H and ζ_TS of artemisinin (Form Ⅰ) in the selected solvents were investigated. The research could give important guiding significance and make a fundamental contribution to enrich and expand the solubility database and thermodynamic mechanism of dissolution and crystallization process of artemisinin (Form Ⅰ).

中文翻译：

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天然植物药青蒿素（I.型）在不同温度下三种二元溶剂中平衡溶解度、Hansen 溶解度参数和建模的研究和评估


青蒿素已在世界各国广泛用于治疗疟疾，挽救了如此多的生命，继续吸引着科研人员的注意。然而，其临床疗效和在其他领域的潜在应用可能会受到其水溶性差的影响。因此，有必要研究青蒿素的溶解度和结晶度。在本研究中，通过重量法测量青蒿素（I.型）在三种二元溶剂（四氢呋喃 + 异丙醇、1,4-二恶烷 + 异丙醇、1,4-二恶烷 + 正丙醇）中的溶解度，从 283.15 K 到 323.15 K。选择 马 模型、理想模型、Jouyban-van′t Hoff 模型和 GSM 模型来拟合获得的溶解度。此外，ARD 、 RMSD 和 RD 用于评估热力学模型的相关可靠性。四种模型的平均 100ARD 和 10⁴RMSD 分别为 2.19 （马）、1.48 （GSM）、2.18 （Jouyban-van′t Hoff）、1.53 （理想）和 12.37 （马）、8.27 （GSM）、11.18 （Jouyban-van′t Hoff）、5.74 （理想）。此外，采用 DSC 、 TGA 、 PXRD 和晶体形态表征分析分析青蒿素溶解过程中的晶体多晶型变化。此外，研究了青蒿素（I.型）在选定溶剂中的汉森溶解度参数和热力学性质，包括 Δ_solH°、Δ_solS°、Δ_solG°、ζ_H 和 ζ_TS。 该研究可为丰富和扩展青蒿素溶解度数据库和热力学机制和青蒿素结晶过程（形式I.）提供重要的指导意义和基础性贡献。