恩诺沙星新盐的制备、表征及溶解性研究

Preparation, Characterization and Solubility of New Enrofloxacin Salt

【目的】制备恩诺沙星(enrofloxacin, ENR)新盐并考察其溶解性,旨在提高ENR的溶解度,丰富其晶体形式。【方法】采用混悬法制备ENR新盐,并通过溶剂挥发法培养其单晶。利用粉末X射线衍射(PXRD)、单晶X射线衍射(SXRD)、傅里叶红外光谱(FTIR)、差示扫描量热分析(DSC)、热失重分析(TGA)和扫描电子显微镜(SEM)对新盐进行一系列表征分析。通过粉末溶解速率试验考察ENR和新盐在37℃、pH 6.8磷酸盐缓冲液中的溶解速率。【结果】制备的ENR新盐为ENR-2,6-二羟基苯甲酸半水合物(ENR-2,6-DHBA·1/2HO)。经单晶结构分析可知,ENR-2,6-DHBA·1/2HO属于三斜晶系,P-1空间群,晶胞参数为:a=13.2495(7)?;b=13.8266(11)?;c=16.0672(8)?;α=114.301°(6);β=90.322°(4);γ=114.438°(7)。不对称单元中包含2个ENR阳离子、2个2,6-DHBA阴离子和1个水分子。2,6-DHBA羧酸基团的质子转移到ENR哌嗪环的N原子上,形成N~+-H…O~-,证实形成的是盐,ENR与HO通过O-H…O氢键连接。FTIR结果证实,2,6-DHBA上的C=O吸收峰由于质子的转移由1 680 cm移动到1 725 cm。新盐的熔点不同于ENR和2,6-DHBA,为253℃。新盐的外貌形态为光滑的棒状。粉末溶解速率曲线显示,ENR-2,6-DHBA·1/2HO平衡时的表观溶解度为0.65 mg/mL,是ENR的1.86倍。【结论】试验成功制备了ENR-2,6二羟基苯甲酸半水合物盐,该盐提高了ENR的溶解度,为提高ENR的生物利用度、增强抗菌效应提供了参考依据。

【Objective】 A new enrofloxacin(ENR) salt was prepared and its solubility was investigated, aiming to improve the solubility of ENR and enrich its crystal form.【Method】 The new ENR salt was prepared by slurry method, and the single crystal was cultivated by slow evaporation method.The new salt was characterized and analyzed by powder X-ray diffraction(PXRD),single crystal X-ray diffraction(SXRD),Fourier transform infrared spectroscopy(FTIR),differential scanning calorimetry(DSC),thermogravimetric analysis(TGA) and scanning electron microscopy(SEM).The dissolution rates of ENR and new salt in pH 6.8 phosphate buffer at 37 ℃ were investigated by powder dissolution rate test.【Result】 The prepared new ENR salt was ENR-2,6-dihydroxybenzoic acid hemihydrate(ENR-2,6-DHBA·1/2 HO).According to the analysis of single crystal structure, ENR-2,6-DHBA·1/2 HO belonged to triclinic crystal system, P-1 space group, and the unit cell parameters were a=13.2495(7)?,b=13.8266(11)?,c=16.0672(8)?,α=114.301°(6),β=90.322°(4),and γ=114.438°(7).The asymmetric unit of new salt contained two ENR cations, two 2,6-DHBA anions and one HO molecule in which a proton was transferred from the carboxyl group of 2,6-DHBA to the nitrogen atom of the piperazine in ENR and formed N-H…O,confirming that the new form was salt.ENR and HO were connected by O-H…O hydrogen bonds.FTIR results indicated that the C=O absorption peak on 2,6-DHBA shifted from 1 680 to 1 725 cmdue to proton transfer.The melting point of the new salt was 253 ℃,different from those of ENR and 2,6-DHBA.The morphology of the new salt was smooth rod-like shape.The powder dissolution rate curve showed that the apparent solubility of ENR-2,6-DHBA·1/2 HO at equilibrium was 0.65 mg/mL,which was 1.86 times that of ENR.【Conclusion】 The results showed that ENR-2,6-dihydroxybenzoic acid hemihydrate salt was successfully prepared.The new salt improved the solubility of ENR,which provided reference basis for improving the bioavailability of ENR and enhancing the antibacterial effect.