\r谢 闯^{1, 2}，郝 菁¹，常芯瑗¹，刘 侃¹，邓鸣峰¹，王静康^{1, 2}

AuthorsHTML:\r谢 闯^{1, 2}，郝 菁¹，常芯瑗¹，刘 侃¹，邓鸣峰¹，王静康^{1, 2}

AuthorsListE:\rXie Chuang^{1, 2}，Hao Jing¹，Chang Xinyuan¹，Liu Kan¹，Deng Mingfeng¹，Wang Jingkang^{1, 2}

AuthorsHTMLE:\rXie Chuang^{1, 2}，Hao Jing¹，Chang Xinyuan¹，Liu Kan¹，Deng Mingfeng¹，Wang Jingkang^{1, 2}

Unit:\r1. 天津大学化工学院，天津 300072；2. 天津化学化工协同创新中心，天津 300072\r
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Unit_EngLish:\r1．School of Chemical Engineering and Technology，Tianjin University，Tianjin 300072，China；
2．Collaborative Innovation Center of Chemical Science and Engineering(Tianjin)，Tianjin 300072，China\r
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Abstract_Chinese:\r吡嗪酰胺(PZA)为最有效的抗结核药物之一，其水溶性差，通过形成共晶的方法可以改善其溶解度，提高药效．本文通过悬浮法制备了PZA 和2，5-二羟基苯甲酸(2，5-DHBA)共晶，产品采用X-射线粉末衍射(PXRD)、差式扫描热分析(DSC)、傅里叶变换红外(FT-IR)和拉曼光谱(Raman)进行表征．结果表明，利用悬浮法可以制备出纯度较高的PZA-2，5-DHBA(1∶1)共晶．进一步采用衰减全反射傅里叶变换红外光谱仪(ATR-FTIR)和在线拉曼光谱等过程分析技术(PAT)，监测并分析了该共晶的形成过程．结果表明，在30,℃下PZA-2，5-DHBA(1∶1)共晶在乙腈中的溶度积为9.4×10-4(mol/L)2；且该过程为PZA 溶解-共晶生成的两步过程，存在成核介稳现象，过程控制步骤为共晶生长．\r
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Abstract_English:\rPyrazinamide(PZA)，one of the most effective antituberculosis drugs，has poor aqueous solubility. By forming cocrystals，its solubility can be improved，which consequently improves its efficacy. In this study，PZA-2,5-dihydroxybenzoic aci (PZA-2,5-DHBA) cocrystal was prepared by slurry crystallization，and the product was characterized by powder X-ray diffraction(PXRD)，differential scanning calorimetry(DSC)，Fourier transform infrared spectroscopy(FT-IR)，and Raman spectrometry. The results showed that the product of slurry crystallization was PZA-2,5-DHBA(1∶1)cocrystal of high purity. Furthermore，the slurry crystallization process was investigated using the process analytical technologies (PATs) of attenuated total reflectance-Fourier transform infrared (ATRFTIR) spectroscopy and in situ Raman spectrometry. The solubility product of PZA-2,5-DHBA cocrystal in acetonitrile at 30℃ was found to be 9.4×10?4 (mol/L)2. The slurry cocrystallization involved two steps：PZA dissolution and crystallization，and a metastable state occurred in nucleation. Moreover，the cocrystal growth was found to be the rate-controlling step.\r
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Keyword_Chinese:共晶；吡嗪酰胺；2，5-二羟基苯甲酸；悬浮结晶；过程分析技术\r

Keywords_English:cocrystal；pyrazinamide(PZA)；2，5-dihydroxybenzoic acid；slurry crystallization；process analytical technology\r


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