头孢拉定双股进料结晶新工艺

摘要

针对头孢拉定反应结晶工艺，设计了双股进料结晶体系，将结晶环境控制在介稳区，有效避免自发成核，操作简单，容易控制。采用单因素法研究了结晶液初始浓度、料液流加速率、搅拌速率、结晶pH值范围、晶种添加量以及养晶时间对结晶产品收率、晶习及粒度分布的影响，确定了优化的工艺参数：结晶液初始浓度（溶质质量/溶剂质量）0.43 g/g，料液流加速率2 mL/min，pH值2.5~2.7，晶种添加量按公式计算，养晶时间60 min，搅拌速率为140 r/min可以得到均匀的棒状晶体，搅拌速率为70 r/min可以得到均匀的簇状聚结体，晶习完整，粒度分布均匀，收率可以达到92%。

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	蒋翠媛
	王平
	刘宝树
	张军立
	孙华

关键词：头孢拉定；反应结晶；双股进料；收率；晶习；粒度分布

Abstract：

The dual feed crystallization was used to control the crystallization environment within the crystallization metastable zone, successfully avoid the spontaneous nucleation, the operation was simple and easy to control. The influences of initial concentration, feeding speed, stirring speed, pH scope, quantity of seed crystal and crystal growing time on the yield, crystal habits and crystal size distribution of products were studied using single factor way. The products were obtained with whole crystal habits and homogeneous size distribution at 0.43 g/g initial concentration, 2 mL/min feeding speed, 2.5~2.7 pH scope, 60 min crystal growing time and the quantity of seed crystal was calculated by equation. In addition, with the stirring speed of 70 or 140 r/min, the cluster crystal or clubbed crystal were obtained, respectively. The yield can reached 92%.

Keywords： cephradine； reactive crystallization； dual feed； yield； crystal habits； crystal size distribution

Received 2016-12-14;

Fund:

河北省自然科学基金（B2015208106）；河北省食品药品安全科技重点项目（ZD2015026）。

Corresponding Authors: 孙华,E-mail:sunhua@hebust.edu.cn。 Email: sunhua@hebust.edu.cn

About author: 蒋翠媛(1992),女,硕士研究生,现从事药物结晶研究。

引用本文:

蒋翠媛, 王平, 刘宝树, 张军立, 孙华.头孢拉定双股进料结晶新工艺[J]. 化学工业与工程, 2018,35(3): 43-49

Jiang Cuiyuan, Wang Ping, Liu Baoshu, Zhang Junli, Sun Hua.The Dual Feed Crystallization Process of Cephradine[J]. Chemcial Industry and Engineering, 2018,35(3): 43-49

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