Benznidazole, the primary drug used in Chagas’ disease treatment, has known side effects, which may limit its widespread use. Its low solubility could negatively interfere in the bioavailability, even accentuating the toxic effects. Cocrystals have been extensively used to modify and optimize physicochemical properties, but, as single-component raw materials, they are susceptible to the phenomenon of polymorphism. In this work, we report a trimorphic cocrystal containing a 1:1 ratio of benznidazole and salicylic acid. The crystalline structures of three polymorphs were elucidated by single-crystal X-ray diffraction. Moreover, several isostructural solvates were also synthesized and analyzed. The same carboxylic acid-imidazole supramolecular heterosynthon is present in the four forms, but the main structural feature is an extended column based on amide–amide hydrogen bonds. On the basis of the crystalline structures, the trimorphic system was classified as conformational and packing polymorphism. Furthermore, the dissolution profiles of the stable forms were determined and showed a significant solubility improvement over the raw material.

中文翻译：

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抗克氏锥虫药物苯甲唑的共晶多晶型物和溶剂化物具有改善的溶解性能

苯甲唑是查加斯病治疗中使用的主要药物，具有已知的副作用，可能会限制其广泛使用。它的低溶解度可能会对生物利用度产生不利影响，甚至加剧毒性作用。共晶体已被广泛用于修饰和优化理化性质，但是作为单组分原料，它们易受多晶现象的影响。在这项工作中，我们报告了一种含有1：1苯并硝唑和水杨酸比例的三晶共晶体。通过单晶X射线衍射阐明了三种多晶型物的晶体结构。此外，还合成和分析了几种同构溶剂化物。相同的羧酸-咪唑超分子杂合子以四种形式存在，但是主要的结构特征是基于酰胺-酰胺氢键的扩展柱。根据晶体结构，将三态系统分类为构象和堆积多态性。此外，确定了稳定形式的溶出曲线，并显示出相对于原料的显着溶解度改善。