Solubility determination and analysis of methimazole in different solvent systems at T = 278.15–323.15 K

Abstract Methimazole is a Commonly used drugs for treatment of hyperthyroidism. Researching the solubility property of methimazole in multifarious solvent systems can be used for optimizing the purification process of methimazole in industry. In this study, the solubility properties of methimazole in twelve pure solvents (methanol, ethanol, 1-propanol, isopropanol, 1-butanol, isobutanol, 1,4-dioxane, methyl acetate, acetonitrile, ethyl acetate, tetrahydrofuran, acetone) and four binary mixed solvents (methanol + ethyl acetate, methanol + acetonitrile, methanol + isopropanol, methanol + methyl acetate) were tested within 278.15 K to 323.15 K under 101.325 kPa. The results show that methimazole has the highest solubility in methanol and the smallest solubility in ethyl acetate. In addition, solubility is positively correlated with temperature in pure solvents and mixed solvents. The XRD spectrum results show that the crystal form of methimazole before and after dissolving in twelve pure solvents do not change. The DSC test shows that the melting point of methimazole is 417.27 K, and it is also proved that methimazole do not decompose before reaching the melting point. Herein, the Modified Apelblat model and Buchowski-Ksiazaczak λh model were used to fit the solubility data of methimazole in pure solvents. Jouyban-Acree model, CNIBS/R-K model and SUN model were used to fit the solubility data of methimazole in binary mixed solvents. The results show that Modified Apelblat model and CNIBS/R–K model have the best correlation with the solubility of methimazole. Analysis using the KAT-LSER model reveals that the influence of the interaction between part of the solvent and solute molecule on solubility. The results show that the impact of dipolarity/polarizability is dominant.