药学学报, 2022, 57(4): 1130-1135
周新波, 刘继永, 俞卡茜, 胡秀荣. 抗癫痫新药布瓦西坦的热膨胀特性研究[J]. 药学学报, 2022, 57(4): 1130-1135.
ZHOU Xin-bo, LIU Ji-yong, YU Ka-xi, HU Xiu-rong. Thermal expansion behaviors of the new antiepileptic drug brivaracetam[J]. Acta Pharmaceutica Sinica, 2022, 57(4): 1130-1135.

周新波1, 刘继永2, 俞卡茜2, 胡秀荣2*
1. 浙江京新药业股份有限公司, 浙江 新昌 312500;
2. 浙江大学化学系, 浙江 杭州 310028
为了研究布瓦西坦晶型I的热膨胀特性,探讨晶体结构对其热膨胀行为的影响机制,采用X射线单晶衍射(SXRD)和变温X射线粉末衍射(VT-PXRD)技术在不同温度下对布瓦西坦晶型I的晶体结构进行了热膨胀研究;用CrystalExplorer 21.5软件,以B3LYP/6-31G (d,p)波函数对布瓦西坦分子进行相互作用能的计算和分析。结果表明,在123~323 K温度范围内,布瓦西坦晶型I呈显著的可逆各向异性热膨胀;膨胀轴(X1X2X3)方向与晶胞轴(abc)方向基本保持一致,膨胀轴的热膨胀系数分别为-127.61×10-6、95.96×10-6、233.80×10-6 K-1,其中a轴呈线性负膨胀,体积热膨胀系数为202.17×10-6 K-1。能量框架可视化结果显示,晶体内分子相互作用层状结构明显,层与层间相互作用能较弱,导致晶胞在c轴方向呈显著的线性正膨胀。通过实验与理论分析相结合的方式,系统分析了布瓦西坦晶型I的热膨胀特性,探究了晶体结构对其热膨胀行为的影响机制,对其在实际中的应用(如制剂工艺研发和生产)具有重要意义。
关键词:    布瓦西坦      热膨胀      黏冲      能量框架      晶体结构     
Thermal expansion behaviors of the new antiepileptic drug brivaracetam
ZHOU Xin-bo1, LIU Ji-yong2, YU Ka-xi2, HU Xiu-rong2*
1. Zhejiang Jingxin Pharmaceutical Co., Ltd., Xinchang 312500, China;
2. Chemistry Department, Zhejiang University, Hangzhou 310028, China
The purpose of the study was to investigate the thermal expansion characteristics of brivaracetam form I, and explore the influence mechanism of the crystal structure on its thermal expansion behavior. The crystal structure of brivaracetam form I was characterized by X-ray single crystal diffraction and variable temperature X-ray powder diffraction at different temperatures. The interaction energy of brivaracetam molecule calculated by B3LYP/6-31G(d,p) wave function with the aid of CrystalExplorer 21.5 software. The results show that brivaracetam form I exhibits significant reversible anisotropic thermal expansion under the temperature range of 123-323 K. The principal expansion X1, X2, X3 axes are approximately aligned with the a, b and c axes of the unit cell, and the thermal expansion coefficients of the principal expansion axes are -127.61×10-6, 95.96×10-6, 233.80×10-6 K-1, respectively. The a-axis exhibits negative expansion characteristics. The volumetric thermal expansion coefficient is 202.17×10-6 K-1. The energy framework of the crystal is obvious layered, and the interaction energy between layers is weak, which leads to a significant linear positive expansion in the c-axis direction of the unit cell. Through a combination of experimental and theoretical methods, the thermal expansion characteristics of brivaracetam form I are systematically analyzed, and the influence mechanism of the crystal structure on its thermal expansion behavior is explored, which has certain guiding significance for the production process of tablet preparations in practice.
Key words:    brivaracetam    thermal expansion    punch sticking    energy framework    crystal structure   
收稿日期: 2021-11-28
DOI: 10.16438/j.0513-4870.2021-1693
通讯作者: 胡秀荣,Tel:86-571-88273491,E-mail:huxiurong@zju.edu.cn
Email: huxiurong@zju.edu.cn
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