With the aim of developing multidrug solids through a tuned crystal engineering approach, we have selected two antiurinary infective drugs, namely, nitrofurantoin (NF) and trimethoprim (TMP) and isolated eight binary drug–drug solid solvates along with a nonsolvated cocrystal. Crystal structure analyses were performed for eight of these solids and rationalized in terms of known supramolecular synthons formed by pyrimidine, imide, and amine functionalities. Notably, the TMP–NF anhydrous cocrystal and its ionic cocrystal hydrate exhibit enhanced equilibrium solubilities compared to pure NF or the simple NF hydrate. Furthermore, the ionic cocrystal hydrate exhibits greater antibacterial activity against the Gram-negative bacteria, E. coli, compared to the parent TMP and NF at the lowest concentration of 3.9 μg/mL. This study indicates initial pathways using the cocrystal methodology that would help to eventually arrive at an antiurinary cocrystal with optimal properties.

中文翻译：

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呋喃妥因和甲氧苄啶的药物-药物二元固体：晶体工程和药物特性。

为了通过调整晶体工程方法开发多药固体，我们选择了两种抗泌尿感染药物，即呋喃妥因 (NF) 和甲氧苄啶 (TMP)，并分离出八种二元药物-药物固体溶剂化物以及一种非溶剂化共晶。对这些固体中的八种进行了晶体结构分析，并根据由嘧啶、酰亚胺和胺官能团形成的已知超分子合成子进行了合理化分析。值得注意的是，与纯 NF 或简单的 NF 水合物相比，TMP-NF 无水共晶及其离子共晶水合物表现出增强的平衡溶解度。此外，离子共晶水合物对革兰氏阴性菌、大肠杆菌表现出更大的抗菌活性，与最低浓度为 3.9 μg/mL 的亲本 TMP 和 NF 相比。这项研究表明了使用共晶方法的初始途径，这将有助于最终获得具有最佳特性的抗泌尿共晶。