| 引用本文: | 吴萍,黄国传,刘文鹏,高庆峰,龚胜,金美英,俞卡茜.不同晶习他克莫司一水合物晶型的表征研究及稳定性考察[J].中国现代应用药学,2022,39(14):1856-1862. |
| WU Ping,HUANG Guochuan,LIU Wenpeng,GAO Qingfeng,GONG Sheng,JIN Meiying,YU Kaxi.Study on the Characterization and Stability of Different Crystal Habits of Tacrolimus Monohydrate[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(14):1856-1862. |
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| 摘要: |
| 目的 对2种不同晶习的他克莫司一水合物晶型(tacro-A和tacro-B)的结构进行表征研究及加速稳定性考察。方法 采用X-射线单晶衍射和X-射线粉末衍射技术结合BFDH模型理论，对晶体结构进行表征研究；通过扫描电镜技术获得2种晶习样品的微观晶体形态；采用6个月加速稳定性试验对2种晶体进行稳定性考察。结果 呈柱状的tacro-B加速稳定性优于呈薄片状的tacro-A，tacro-B在6个月加速稳定性考察下无新增杂质。结论 在保持药物内部结构(即晶型)不变的情况下，通过调节其外部结构(如晶习)，也是改变药物性质如溶解性、稳定性的重要途径，值得研究和关注。 |
| 关键词: 他克莫司 晶习 晶体结构 稳定性 |
| DOI：10.13748/j.cnki.issn1007-7693.2022.14.010 |
| 分类号:R917.101 |
| 基金项目:浙江省科技计划项目(2019C03087) |
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| Study on the Characterization and Stability of Different Crystal Habits of Tacrolimus Monohydrate |
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WU Ping1, HUANG Guochuan1, LIU Wenpeng1, GAO Qingfeng1, GONG Sheng1, JIN Meiying1, YU Kaxi2
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1.Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd., Hangzhou 310011, China;2.Department of Chemistry, Zhejiang University, Hangzhou 310028, China
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| Abstract: |
| OBJECTIVE To study the structure characterization and accelerated stability of tacrolimus monohydrate (tacro-A and tacro-B) with different crystal habits. METHODS The crystal structure was characterized by X-ray single crystal diffraction and X-ray powder diffraction combined with BFDH model theory. The micro crystal morphology of the two samples were obtained by scanning electron microscopy. The stability of the two crystals were investigated by 6-month accelerated stability test. RESULTS The column shape tacro-B was better than the sheet shape tacro-A in the accelerated stability test, and there was no new impurity in tacro-B after 6 months of accelerated stability test. CONCLUSION It is an important way to change the drug properties such as solubility and stability by adjusting its external structure (such as crystal habit) while keeping the internal structure (i.e. crystal form) unchanged. |
| Key words: tacrolimus crystal habit crystal structure stability |
