Furosemide Cocrystals: Structures, Hydrogen Bonding, and Implications for Properties
Furosemide Cocrystals: Structures, Hydrogen Bonding, and Implications for Properties
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DOI：
10.1021/cg401662d
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发表时间：
2014-02-01
影响因子：
3.8
通讯作者：
Evans, Ivana Radosavljevic
中科院分区：
文献类型：
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作者：
Harriss, Bethany I.;Vella-Zarb, Liana;Evans, Ivana Radosavljevic
本文报道了呋塞米（4-氯-2-[（2-呋喃基甲基）氨基]-5-氨磺酰基苯甲酸）的四种共晶的晶体生长。呋塞米是一种用于治疗高血压和水肿的袢利尿药，由对氨基苯甲酸、烟酰胺和异烟酰胺作为共晶体制备而成。我们提出了四种新的晶体结构，并阐明了存在于共晶中的分子间相互作用。结构显示有趣的超分子化学：一些不同的质子，以及短的强氢键与部分质子转移和质子紊乱的迹象。使用粉末X-射线衍射，固态NMR和热分析，我们提供的证据为两种组合物，即1：1共晶体的呋塞米和对氨基苯甲酸和2：1共晶体的呋塞米和异烟酰胺的散装样品的制备，突出了这种多技术的方法来表征有机固体（包括共晶体和溶剂化物）通过研磨方法制备的一般必要性。最后，我们关联的结构特征首次在这项工作中与先前公布的呋塞米共晶的相关性质（溶解度和内在的溶解速率）。
In this paper, we report the crystal growth of four cocrystals of furosemide (4-chloro-2-[(2-furanylmethyl)amino]-5-sulfamoylbenzoic acid), a loop diuretic drug used for the treatment of hypertension and edemas, prepared with p-aminobenzoic acid, nicotinamide, and isonicotinamide as coformers. We present four new crystal structures and elucidate the intermolecular interactions present in the cocrystals. The structures display interesting supramolecular chemistry: a number of different synthons, as well as short strong hydrogen bonds with partial proton transfer and indications of proton disorder. Using powder X-ray diffraction, solid state NMR, and thermal analysis, we provide evidence for the preparation of bulk samples of two compositions, namely, the 1:1 cocrystal of furosemide and p-aminobenzoic acid and 2:1 cocrystal of furosemide and isonicotinamide, highlighting the general necessity of such multitechnique approaches to characterize organic solids (including cocrystals and solvates) prepared by grinding methods. Finally, we correlate the structural features reported for the first time in this work with the previously published pharmacologically relevant properties (solubility and intrinsic dissolution rate) of the furosemide cocrystals.