Polymorphic Solubility Ratio of Famotidine and Sulfathiazole in Various Solvents
Polymorphic Solubility Ratio of Famotidine and Sulfathiazole in Various Solvents
复制标题
法莫替丁和磺胺噻唑在各种溶剂中的多晶型溶解度比
DOI：
10.1021/acs.cgd.1c00064
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发表时间：
2021
影响因子：
3.8
通讯作者：
Yoda Satoshi
中科院分区：
文献类型：
--
作者：
Takebayashi Yoshihiro;Sue Kiwamu;Furuya Takeshi;Yoda Satoshi
在298.15 K下测量了法莫替丁的两种多晶型物（A，B）和磺胺噻唑的三种多晶型物（I，II和IV）在各种溶剂中的溶解度，以澄清溶解度比B/A，I/IV和II/IV如何取决于溶剂。对于两种多晶型物，法莫替丁溶解度以乙酸乙酯<水< 2-丙醇<乙腈< 1-丙醇<乙醇<丙酮<甲醇的顺序增加。溶解度比B/A在1.09 ~ 1.32之间变化，与溶剂极性呈正相关。相反，磺胺噻唑的溶解度以水<乙酸乙酯< 2-丙醇< 1-丙醇<乙醇<甲醇的顺序增加。溶解度比I/IV和II/IV分别在1.62 ± 0.04和1.00 ± 0.03范围内变化不大。可忽略的溶剂依赖性表明溶解度比仅由固态下多晶型物之间的自由能差决定。这使我们能够估计亚稳态形式I在水、甲醇和乙醇中的溶解度，由于溶剂介导的转化，这是无法测量的。的溶解度比进行了比较，使用三种类型的热力学方程计算的转变温度和焓变差示扫描量热法测量。Hoffmann提出的方程给出了最接近实验结果的值。
Solubilities of two polymorphs of famotidine (A, B) and three polymorphs of sulfathiazole (I, II, and IV) were measured in various solvents at 298.15 K to clarify how the solubility ratios B/A, I/IV, and II/IV depend on the solvent. The famotidine solubility increased in the order of ethyl acetate < water < 2-propanol < acetonitrile < 1-propanol < ethanol < acetone < methanol for both polymorphs. The solubility ratio B/A varied from 1.09 to 1.32, having a positive correlation with the solvent polarity. In contrast, the sulfathiazole solubility increased in the order of water < ethyl acetate < 2-propanol < 1-propanol < ethanol < methanol. The solubility ratios I/IV and II/IV changed little within 1.62 ± 0.04 and 1.00 ± 0.03, respectively. The negligible solvent dependence indicates that the solubility ratios are determined only by the free energy difference between the polymorphs in the solid state. This enabled us to estimate the solubilities of metastable form I in water, methanol, and ethanol, which could not be measured due to solvent-mediated transformation. The solubility ratios were compared with those calculated using three types of thermodynamic equations from the transition temperature and enthalpy change measured by differential scanning calorimetry. The equation proposed by Hoffmann gave the values closest to the experimental results.