千克级非布司他晶型A制备工艺  

Kilogram-scale Preparation of Febuxostat Crystal Form A

作　　者：宋航 杨汉跃 闫显光 曾银海 李润莱 李树安 SONG Hang;YANG Hanyue;YAN Xianguang;ZENG Yinhai;LI Runlai;LI Shu'an(School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005;Jiangsu Deyuan Pharmaceutical Co.,Ltd.,Lianyungang 222047;School of Polymer Science and Engineering,Sichuan University,Chengdu 610065)

机构地区：[1]江苏海洋大学药学院,江苏连云港222005 [2]江苏德源药业股份有限公司,江苏连云港222047 [3]四川大学高分子科学与工程学院,四川成都610065

出　　处：《中国医药工业杂志》2022年第3期388-394,共7页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金青年基金(52103042);江苏省苏北科技专项(SZ-LYG202017);江苏省研究生科研与实践创新计划项目(SJCX20-1219、KYCX20-2958、KYCX20-2960)。

摘　　要：通过晶型转化试验研究了非布司他晶型A实验室及千克级放大制备方法。用正交试验考察了溶剂种类、溶剂用量、溶解温度、析晶温度、析晶时间等因素对非布司他晶型形成和收率的影响。优化工艺为:在75℃条件下,非布司他溶解于8倍量(w/v)的无水乙醇中,10 min后缓慢(0.5~1.0℃/min)冷却至10℃,低速(100 r/min以下)搅拌析晶4 h,收率93%~96%,溶剂可循环利用2次。本工艺制备非布司他晶型A操作简单、安全环保、析晶时间短,有利于工业化。Based on the crystalline form transformation,preparation of febuxostat crystal form A in both laboratory-and kilogram-scales were investigated.Orthogonal experiments were employed to distinguish the effects of solvents and dosage,dissolving temperature,crystallization temperature and time,and other factors on formation and yield of febuxostat crystal form A yield.The optimized process was as follows:febuxostat was dissolved in 8 times of absolute ethanol at 75 ℃ for 10 min,then the solution was slowly cooled to 10 ℃ at 0.5-1 ℃/min,followed by stirring for 4 h at a low speed(below 100 r/min) to form febuxostat crystal form A precipitate with the yield of 93%-96%;the solvent could be recycled twice.This preparation approach of febuxostat crystal form A with short crystallization time was facile,robust,and environmentally friendly,which was suitable for industrialization.

关 键 词：非布司他 晶型A 千克级制备 溶剂循环利用 晶型转化 

分 类 号：R971.1[医药卫生—药品]