In this work, the dissolution behavior of a novel pharmacological factor, 3-methylflavone-8-carboxylic acid (MFCA) in different solvents was studied. Firstly, the solubility of MFCA in ten mono-solvents (acetonitrile, tetrahydrofuran, acetone, N,N-dimethylformamide, methyl acetate, ethyl acetate, butyl acetate, methanol, ethanol and isobutanol) and three binary solvents (N,N-dimethylformamide + acetonitrile, tetrahydrofuran + acetonitrile, methyl acetate + acetonitrile) at different temperatures (273.15–323.15 K) was determined by static equilibrium-high performance liquid chromatography. The experimental results showed that the solubility of MFCA increased with increasing temperature in tested solvents, and the solubility of MFCA in N,N-dimethylformamide was maximal. The Hansen solubility parameter was used to research the dissolution behavior of MFCA. Meanwhile, the solvent effect was discussed by KAT-LSER model in ten mono-solvents, and it was found that the hydrogen bond basicity and nonspecific dipolarity/polarizability were favorable to the dissolution of MFCA. In addition, modified Apelblat model, model, CNIBS/R-K model and Jouyban-Acree model were used to analyze the correlation and evaluate the applicability for the experimental solubility data of MFCA. The calculated data showed that modified Apelblat model and CNIBS/R-K model are the best models for mono and binary solvents, respectively. Finally, the dissolution thermodynamic properties of MFCA were studied by van't Hoff analysis, indicating that the dissolution of MFCA was an endothermic and entropic driven process. To sum up, these experimental results could provide pretty reference for purification and crystallization optimization of MFCA, and realize the industrial large-scale production of various drugs such as diuretic.

中文翻译：

---

3-甲基黄酮-8-甲酸在不同溶剂中的汉森溶解度参数、溶剂效应及热力学性质研究


在这项工作中，研究了一种新型药理因子3-甲基黄酮-8-羧酸（MFCA）在不同溶剂中的溶出行为。首先，MFCA在十种单溶剂（乙腈、四氢呋喃、丙酮、N,N-二甲基甲酰胺、乙酸甲酯、乙酸乙酯、乙酸丁酯、甲醇、乙醇和异丁醇）和三种二元溶剂（N,N-二甲基甲酰胺+采用静态平衡-高效液相色谱法测定不同温度（273.15–323.15 K）下的乙腈、四氢呋喃+乙腈、乙酸甲酯+乙腈。实验结果表明，MFCA在测试溶剂中的溶解度随着温度的升高而增加，其中MFCA在N,N-二甲基甲酰胺中的溶解度最大。 Hansen溶解度参数用于研究MFCA的溶出行为。同时，利用KAT-LSER模型讨论了10种单一溶剂中的溶剂效应，发现氢键碱性和非特异性偶极/极化性有利于MFCA的溶解。此外，采用修正的Apelblat模型、模型、CNIBS/R-K模型和Jouyban-Acree模型对MFCA的实验溶解度数据进行相关性分析并评价其适用性。计算数据表明，修正的Apelblat模型和CNIBS/R-K模型分别是一元和二元溶剂的最佳模型。最后，通过van't Hoff分析研究了MFCA的溶解热力学性质，表明MFCA的溶解是一个吸热和熵驱动的过程。 综上所述，这些实验结果可为MFCA的纯化和结晶优化提供很好的参考，并实现利尿剂等多种药物的工业化规模化生产。