Insights into the Structure of Sucralfate by Advanced Solid- and Liquid-State NMR,Molecular Pharmaceutics

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Insights into the Structure of Sucralfate by Advanced Solid- and Liquid-State NMR
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2024-02-08 , DOI: 10.1021/acs.molpharmaceut.3c01042
Chaithanya Hareendran _{1,

2} , Sapna Ravindranathan _{1,

2} , T G Ajithkumar _{1,

2}

Affiliation

Sucralfate, which is a sucrose octasulfate aluminum complex, is an active pharmaceutical ingredient (API) falling in the category of cytoprotective agents which are very effective for gastric and duodenal ulcers. On interaction with stomach acid, it ionizes into aluminum and sucrose octasulfate ions to form a protective layer over the ulcerated region inhibiting further attack from acid. The mechanism of action of sucralfate in the context of its structure is not well understood. Considering that at least two forms of this API are available in the market, there are no reports on the various forms of sucralfate and differences in their pharmacological action. We characterized the two forms of sucralfate using multinuclear, multidimensional solid-state NMR, and the results show significant structural differences between them arising from variation in the aluminum environment and the level of hydration. The impact of structural differences on pharmacological action was examined by studying acid-induced Al release by ²⁷Al liquid-state NMR. The sucralfate, European pharmaceutical standard, Form I, undergoes faster disruption in acid compared to Form II. The difference is explained on the basis of structural differences in the two forms which gives significant insights into the action of sucralfate in relation to its structure.

中文翻译：

通过先进的固态和液态 NMR 深入了解硫糖铝的结构

硫糖铝是一种蔗糖八硫酸铝络合物，是一种活性药物成分 (API)，属于细胞保护剂类别，对胃和十二指肠溃疡非常有效。在与胃酸相互作用时，它电离成铝和蔗糖八硫酸根离子，在溃疡区域形成保护层，抑制酸的进一步攻击。硫糖铝的作用机制及其结构尚不清楚。考虑到市场上至少有两种形式的该原料药，目前还没有关于硫糖铝的各种形式及其药理作用差异的报道。我们使用多核、多维固态核磁共振对两种形式的硫糖铝进行了表征，结果显示，由于铝环境和水合水平的变化，它们之间存在显着的结构差异。通过²⁷ Al 液态 NMR 研究酸诱导的 Al 释放，检查结构差异对药理作用的影响。与 II 型相比，硫糖铝（欧洲制药标准 I 型）在酸中的分解速度更快。这种差异是根据两种形式的结构差异来解释的，这为了解硫糖铝与其结构相关的作用提供了重要的见解。

更新日期：2024-02-08

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