溶剂对普拉格雷硫酸氢盐多晶型形成的影响规律  

Effect of solvent on polymorph formation of prasuggr 1 hydrogen sulfate

作　　者：赵佳敏 程鹏高 杜威 唐娜 王栋 ZHAO Jia-min;CHENG Peng-gao;DU Wei;TANG Na;WANG Dong(School of Chemical Engineering and Materials,Tianjin University of Science and Technology,Tianjin 300457,China)

机构地区：[1]天津科技大学化工与材料学院,天津300457

出　　处：《中国新药杂志》2023年第8期847-852,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金青年基金资助项目(21506162);天津市自然科学基金青年基金资助项目(17JCQNJC13200)。

摘　　要：目的:为确定普拉格雷游离碱和浓硫酸反应结晶过程中普拉格雷硫酸氢盐多晶型形成的关键影响因素,阐明溶剂和过饱和度等对其多晶型形成的影响规律,揭示普拉格雷硫酸氢盐的反应结晶机制。方法:本文以普拉格雷硫酸氢盐为研究对象,聚焦其结晶热力学和反应结晶过程,基于X-射线衍射光谱(PXRD)、差示扫描量热(DSC)和热重分析(TGA)的联合应用,探究普拉格雷硫酸氢盐多晶型间的稳定性关系和反应结晶过程多晶型形成的影响规律。结果:通过多晶型热力学性质和反应结晶过程分析,结果表明溶剂和过饱和度是影响多晶型形成过程的关键因素。结论:普拉格雷硫酸氢盐晶型Ⅰ和晶型Ⅱ是单变体系,且晶型Ⅱ是稳定晶型,溶剂在其多晶型形成过程中起主导作用,在仲丁醇中其多晶型的形成符合Ostwald规则。Objective:To determine the key influencing factors on formation of prasugrel hydrogen sulfate polymorph during the reactive crystallization of prasugrel free alkali and sulfuric acid,clarify the rule of the influences of solvent,temperature,and supersaturation,and reveal the mechanism of prasugrel hydrogen sulfate polymorph formation.Methods:Based on combined application of X-ray diffraction spectroscopy(PXRD),differential scanning calorimetry(DSC)and thermogravimetric analysis(TGA),this study focused on the crystallization thermodynamics and reactive crystallization process of prasugrel hydrogen sulfate.The stability relationship between the polymorphs of prasugrel hydrogen sulfate and the influencing rule of polymorph formation during reaction crystallization were investigated.Results:It was shown that solvent and supersaturation were the key factors affecting the formation of prasugrel hydrogen sulfate polymorphs.Conclusion:Prasugrel hydrogen sulfate form Ⅰ and form Ⅱ are monotropically related systems,and form Ⅱ is a stable form.Solvent plays a leading role in the formation of prasugrel hydrogen sulfate polymorphs,and the formation of polymorphs in butanol obeys to the Ostwald's rule.

关 键 词：普拉格雷硫酸氢盐 多晶型 溶剂 X-射线衍射分析 热重分析 

分 类 号：R914[医药卫生—药物化学]