Preparation and Physiochemical Analysis of Novel Ciprofloxacin / Dicarboxylic Acid Salts.
Preparation and Physiochemical Analysis of Novel Ciprofloxacin / Dicarboxylic Acid Salts.
复制标题
新型环丙沙星/二羧酸盐的制备和理化分析。
DOI：
10.1016/j.xphs.2022.08.008
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发表时间：
2023
影响因子：
3.8
通讯作者：
Hibbard T
中科院分区：
文献类型：
--
作者：
Hibbard T
报道了用机械力化学合成法和溶剂结晶法合成的4种物化性能得到改善的新型环丙沙星二元酸盐(CFX)的晶体结构。选择了一系列分子量增加的二元酸，预测它们通过一种羧酸：仲胺合成子相互作用。它们是琥珀酸(SA)、戊二酸(GA)、己二酸(AA)和松香酸(PA)(分别为4、5、6、7个碳原子)。通过单晶和粉末X-射线衍射、傅里叶变换红外光谱、热重分析、差示扫描量热法、扫描电子显微镜和水溶解度测定对其进行了表征，表明这些盐具有与环丙沙星碱不同的物理化学性质。通过剑桥结构数据库(CSD)的检索，确认CFX-SA、CFX-GA、CFX-AA和CFX-PA为新的晶体结构。此外，GA盐的溶解度大大高于广泛使用的一水盐酸盐(CFX-HCl·H2O)。CFX-SA、CFX-GA和CFX-AA的最小抑菌浓度为0.008 g/L，CFX-PA的最小抑菌浓度为0.004 g/L，所制备的CFX盐具有与CFX-HCl·H2O相当的抑菌活性。这些盐对增加CFX在传统口服制剂之外的应用具有积极意义，并强调机械力化学活化是合适的生产方法。
The crystal structures of four novel dicarboxylic acid salts of ciprofloxacin (CFX) with modified physicochemical properties, prepared by mechanochemical synthesis and solvent crystallization, are reported. A series of dicarboxylic acids of increasing molecular weight was chosen, predicted to interact via a carboxylic acid:secondary amine synthon. These were succinic (SA), glutaric (GA), adipic (AA) and pimelic (PA) acids (4, 5, 6, 7 carbon atoms respectively). Characterized by single crystal and powder X-ray diffraction, Fourier-Transform Infrared Spectroscopy, thermogravimetric analysis, differential scanning calorimetry, scanning electron microscopy and aqueous solubility measurements, these salts showed distinct physicochemical properties relative to ciprofloxacin base. Searches of the Cambridge Structural Database (CSD) confirmed CFX-SA, CFX-GA, CFX-AA and CFX-PA to be novel crystal structures. Furthermore, the GA salt has substantially higher solubility than the widely available hydrochloride monohydrate salt (CFX-HCl·H2O). CFX-SA, CFX-GA and CFX-AA showed minimum inhibitory concentration (MIC) of 0.008 g/L and CFX-PA showed MIC of 0.004 g/L. The prepared CFX salts retained antibacterial activity exhibiting equivalent antimicrobial activity to CFX-HCl·H2O. These salts have positive implications for increasing the application of CFX beyond conventional oral formulations and highlight mechanochemical activation as suitable production method.