Naveena S. Veeranagaiah, Madhu Rana, Battini Swapna, Raghavaiah Pallepogu* and Ashwini K. Nangia*,
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引用次数: 0
Abstract
Ethionamide (ETH) is a second-line antituberculosis drug, but its aqueous solubility is poor. A cocrystal/salt screen of ETH with fluorobenzoic acid (FBA) coformers afforded four cocrystals and one salt of ETH, namely, ETH-4-fluorobenzoic acid (4FBA, cocrystal), ETH-3,4-difluorobenzoic acid (34DFBA, cocrystal), ETH-2,4,5-trifluorobenzoic acid (245TFBA, cocrystal), ETH-2,3,4,5-tetrafluorobenzoic acid (2345TFBA, cocrystal), and ethionamidium-2-fluoro-6-hydroxybenzoate (2F6HBA, salt). The new crystalline multicomponent cocrystal-salt (MCCS) forms were characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, single crystal X-ray diffraction, and FT-IR analysis. Structural analysis showed that the acid-pyridine, hydroxyl-pyridine, and thioamide dimer synthons stabilize ETH cocrystals/salt structures. The cocrystals/salt exhibit remarkable improvement in solubility, dissolution, and diffusion at pH 7 in phosphate buffer solution. The ability of fluoro compounds to increase membrane diffusion and bioavailability of drugs as MCCS complexes may be of general applicability for poor solubility and permeability drugs.
乙硫酰胺（ETH）是一种二线抗结核药物，但其水溶性较差。通过对 ETH 与氟苯甲酸（FBA）共聚物的共晶体/盐筛选，得到了 ETH 的四种共晶体和一种盐，即 ETH-4-氟苯甲酸（4FBA，共晶体）、ETH-3,4-二氟苯甲酸（34DFBA、共晶体）、ETH-2,4,5-三氟苯甲酸（245TFBA，共晶体）、ETH-2,3,4,5-四氟苯甲酸（2345TFBA，共晶体）和 2-氟-6-羟基苯甲酸乙脒（2F6HBA，盐）。通过粉末 X 射线衍射、差示扫描量热法、热重分析、单晶 X 射线衍射和傅立叶变换红外分析，对新型结晶多组分共晶盐（MCCS）进行了表征。结构分析表明，酸性吡啶、羟基吡啶和硫酰胺二聚体合成物稳定了 ETH 共晶体/盐结构。在 pH 值为 7 的磷酸盐缓冲溶液中，共晶体/盐的溶解度、溶解性和扩散性都有显著改善。氟化合物作为 MCCS 复合物能够增加药物的膜扩散和生物利用度，这对于溶解性和渗透性较差的药物可能具有普遍适用性。
期刊介绍：
The aim of Crystal Growth & Design is to stimulate crossfertilization of knowledge among scientists and engineers working in the fields of crystal growth, crystal engineering, and the industrial application of crystalline materials.
Crystal Growth & Design publishes theoretical and experimental studies of the physical, chemical, and biological phenomena and processes related to the design, growth, and application of crystalline materials. Synergistic approaches originating from different disciplines and technologies and integrating the fields of crystal growth, crystal engineering, intermolecular interactions, and industrial application are encouraged.
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