Solubility determination and thermodynamic modelling of verapamil hydrochloride in methanol-water binary solvent systems from 293.15 K to 323.15 K

Keshava Jetha , Rizwan Ghumara , Chirag Patel , Praful Bharadia , Ravibhai Bhola
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Abstract

Verapamil Hydrochloride is a key calcium channel blocker used to treat cardiovascular disorders and prevent cluster headaches by inhibiting calcium influx, thus improving cardiovascular health. The solubility of Verapamil Hydrochloride (VH) in methanol + water binary solvent systems were studied using a gravimetric method at temperatures from 293.15 K to 323.15 K under atmospheric pressure. The solubility increased with temperature and methanol content, with the highest mole fraction solubility at a 0.90 methanol mole fraction and the lowest at 0.10. Various models, including Apelblat, Van't Hoff, modified Jouyban–Acree, and CNIBS/R-K, were used to calculate theoretical solubility, with RAD and RMSD assessing the model accuracy. Thermodynamic analysis indicated that VH dissolution is endothermic and entropy-driven. This data is valuable for optimizing VH purification and crystallization processes in the pharmaceutical industry.

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盐酸维拉帕米在 293.15 K 至 323.15 K 甲醇-水二元溶剂体系中的溶解度测定和热力学建模
盐酸维拉帕米是一种重要的钙通道阻滞剂,通过抑制钙离子流入治疗心血管疾病和预防丛集性头痛,从而改善心血管健康。采用重量法研究了盐酸维拉帕米(VH)在甲醇+水二元溶剂体系中的溶解度,实验温度为 293.15 K 至 323.15 K,实验条件为常压。溶解度随温度和甲醇含量的增加而增加,甲醇摩尔分数为 0.90 时溶解度最高,甲醇摩尔分数为 0.10 时溶解度最低。计算理论溶解度时使用了多种模型,包括 Apelblat、Van't Hoff、修正的 Jouyban-Acree 和 CNIBS/R-K,并用 RAD 和 RMSD 评估模型的准确性。热力学分析表明,VH 的溶解是内热和熵驱动的。这些数据对于优化制药业中的 VH 纯化和结晶过程非常有价值。
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