摘要
目的:开发抗丙肝药达卡他韦二盐酸盐晶型A的放大制备方法。方法:运用溶液结晶法研究了达卡他韦二盐酸盐晶型A的结晶工艺,包括溶剂的选择、结晶起始温度、熟化时间和结晶终点温度等因素。结果:选定水作为结晶溶剂,结晶起始温度为60℃,60℃熟化时间为6~8小时,终点结晶温度为20~25℃,获得最终产品。100克放大验证结果表明,使用本研究确定的工艺路线,可将晶型A成功放大到100克。结论:建立了达卡他韦二盐酸盐晶型A的放大制备方法,该方法操作简单,所用结晶溶剂为纯水,绿色环保无污染,可放大性好,适合工业化生产。
Objective: The aim of this article is to study the crystallization process of daclatasvir dihydrochloride Form A. Methods: Solution crystallization process was conducted for daclatasvir dihydrochloride Form A. Varied factors including solvent selection, starting temperature, aging time, final temperature were studied. Results: the crystallization process was carried out using water as reaction solvent, 60 ℃ as starting temperature, aging for 6~8 hours at 60 ℃, 20~25 ℃ as the final temperature. The developed crystallization process has been validated on 100 g scale successfully. Conclusion: The crystallization process of Daclatasvir dihydrochloride Form A is set up and it is simple operation, green and pollution-free and suitable for industrial production.
作者
杨朝惠
张龙
汪建明
陈敏华
Yang Chaohui;Zhang Long;Wang Jianming;Chen Minhua(School of Pharmaceutical Sciences, College of Pharmacy, Wuhan University, Wuhan430000;Department of Solid-state Research, Crystal Pharmaceutical Co., Ltd., Suzhou215000, China)
出处
《广东化工》
CAS
2019年第12期4-6,共3页
Guangdong Chemical Industry
关键词
达卡他韦
结晶工艺
溶液结晶
daclatasvir
crystallization process
solution crystallization
