The solubility of eplerenone (EP) in 13 pure solvents (acetonitrile, N,N-dimethylformamide (DMF), acetone, 2-butanone, 4-methyl-2-pentanone, ethyl formate, methyl acetate, ethyl acetate, propyl acetate, butyl acetate, methyl propionate, ethyl propionate, ethanol, and 1-propanol) was determined by the gravimetric method at atmospheric pressure and various temperatures (from 283.15 to 323.15 K). The results showed that the solubility of EP in the selected solvents was positively correlated with the thermodynamic temperature, and the order of solubility of EP at 298.15 K was acetonitrile > DMF > 2-butanone > methyl acetate > 4-methyl-2-pentanone > methyl propionate > ethyl acetate > propyl acetate > ethyl formate > acetone > butyl acetate > ethanol >1-propanol. The modified Apelblat model, van’t Hoff model, λh model, and polynomial empirical model were used for fitting the solubility data, and then the λh model was found to have the highest fitting accuracy with a minimum ARD of 7.0 × 10^–3 and a minimum RMSD of 6.1 × 10^–6. The solvent effect between the solute and the solvent was analyzed using linear solvation energy relationship (LSER), and the enthalpy of solvation (Δ_solH°), entropy of solvation (Δ_solS°), and Gibbs free energy of solvation (Δ_solG°) of the dissolution process of EP were calculated by the van’t Hoff model, which indicated that the dissolution process of EP in the selected solvents was endothermic, nonspontaneous, and entropy-increasing. In this work, the solubility, dissolution characteristics, and thermodynamic parameters of EP were studied, which will provide data support for the production, crystallization, and purification of EP and will provide important guidance for the crystallization optimization of EP in industry.

中文翻译：

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283.15 至 323.15 K 温度下依普利酮在 13 种纯溶剂中的热力学分析


依普利农 (EP) 在 13 种纯溶剂（乙腈、N,N-二甲基甲酰胺 (DMF)、丙酮、2-丁酮、4-甲基-2-戊酮、甲酸乙酯、乙酸甲酯、乙酸乙酯、乙酸丙酯、丁酯）中的溶解度在大气压和不同温度（283.15 至 323.15 K）下通过重量分析法测定乙酸、丙酸甲酯、丙酸乙酯、乙醇和 1-丙醇。结果表明，EP在所选溶剂中的溶解度与热力学温度呈正相关，298.15 K时EP的溶解度顺序为乙腈>DMF>2-丁酮>乙酸甲酯>4-甲基-2-戊酮>丙酸甲酯>乙酸乙酯>乙酸丙酯>甲酸乙酯>丙酮>乙酸丁酯>乙醇>1-丙醇。采用修正的Apelblat模型、van't Hoff模型、λh模型和多项式经验模型对溶解度数据进行拟合，发现λh模型拟合精度最高，ARD最小为7.0×10 ^–3 且最小 RMSD 为 6.1 × 10 ^–6 。利用线性溶剂化能关系(LSER)、溶剂化焓(Δ _sol H°)、溶剂化熵(Δ _sol 采用van't Hoff模型计算了EP溶解过程的吉布斯溶剂化自由能(Δ _sol G°)，表明EP在所选溶剂中的溶解过程是吸热的、非自发的且熵增加的。 本工作对EP的溶解度、溶出特性和热力学参数进行了研究，为EP的生产、结晶和纯化提供数据支持，并为工业上EP的结晶优化提供重要指导。