头孢羟氨苄单水合物反应结晶工艺优化  

Optimization of cefadroxil monohydrate reactive crystallization process

作　　者：龚俊波[1,2] 侯静美[1] 刘胜[1] 董伟兵[1,2] 张军立 

机构地区：[1]天津大学化工学院国家工业结晶工程技术研究中心,天津300072 [2]天津大学现代药物传递及功能高效化天津市重点实验室,天津300072 [3]华北制药集团倍达有限公司,石家庄052165

出　　处：《中国抗生素杂志》2012年第4期280-283,共4页Chinese Journal of Antibiotics

基　　金：天津市面上基金(No.10JCYBJCl4200);天津市重点基金(No.09JCZDJC20100);国家自然科学基金(No.21176173)

摘　　要：利用头孢羟氨苄N,N-二甲基甲酰胺(DMF)溶剂化物在水溶液中反应结晶得到头孢羟氨苄单水合物晶体,产品往往存在聚结、松紧密度小、粒度分布不均匀、晶习不稳定等问题。本文考察了结晶过程中温度、搅拌速率、溶剂配比、溶液pH值等因素对产品粒度分布、晶习及晶体聚结的影响。研究结果表明,结晶温度对产品粒度、晶习和晶体聚结都有影响,搅拌速率和溶剂配比主要影响产品的粒度分布。实验优化得到了头孢羟氨苄单水合物反应结晶的最佳操作工艺并为工业化生产提供了重要的参考价值,利用该工艺得到的头孢羟氨苄单水合物产品为四方片状晶体、晶习完整、粒度分布均匀、产品不聚结,松紧密度分别为0.37g/mL和0.57g/mL,产品质量达国际水平。In the light of the outstanding problems existing in industrialized production of cefadroxil monohydrate by reactive crystallization, such as product crystal agglomeration, low elastic density, terrible crystal size distribution and variable crystal habit, this paper evaluated the effect of several parameters during crystallization process, such as effect of temperature, stirring speed and solvent volume ratio on crystal size distribution, crystal habit and agglomeration of the product. The experimental results showed that crystallization temperature exerted great influence on crystal size, crystal habit and agglomeration of the product. Product crystal size distribution were more susceptible to stirring speed and solvent volume ratio. Optimum crystallization technology of cefadroxil monohydrate were achieved through experiments, by which the product with perfect sheet-like crystal, narrow crystal size distribution, no agglomeration and elastic density 0.37g/mL and 0.57g/mL was prepared. And, the product quality is up to international requirement.

关 键 词：头孢羟氨苄 晶习 反应结晶 聚结 粒度分布 

分 类 号：TQ026.5[化学工程]