头孢克肟溶析结晶过程球形生长机理探究

摘要

采用溶析结晶制备得到头孢克肟的球形结晶，通过对结晶温度、溶质浓度以及盐酸滴加速率等过程参数的考察，提高了产品的流动性、粒度分布及堆密度等参数。针对球形晶体稳定性方面存在的问题，在结晶过程中不同时间点取样分析，确定了过程中无定形的存在及最终产品的晶型。根据实验现象推测头孢克肟在溶析结晶过程中的生长机理，并通过各种表征手段（X射线粉末衍射、扫描电子显微镜等）证明头孢克肟球形结晶的形成是通过内核上多方向的发散生长，而不是通过细晶的聚结。通过在低过饱和度下加入晶种的方式，抑制了结晶过程中无定形的形成，提高了球形晶体的稳定性。

	Service

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	Email Alert
	RSS
	作者相关文章
	宋晓鹏
	屠民海
	龚俊波

关键词：头孢克肟；溶析结晶；球形生长；机理

Abstract：

Spherical products of cefixime were prepared by anti-solvent crystallization and the properties such as bulk density, size distribution and purity of the products were improved by optimizing the process parameters. Considering the instability of the spherical products, in situ sampling method was used to confirm the amorphous nucleation and the crystal morphology of the final spherical products. The assumption of anti-solvent crystallization mechanism for cefixime was proposed and various characterization methods such as X-ray powder diffraction and scanning electron microscope were used to prove that the formation of spherical cefixime crystal is a result of multidirectional growth arising from a central precursor, rather than the aggregation of fine crystals. Finally, the formation of amorphous was inhibited by adding seeds under low degree of supersaturation and as a result, the stability of the spherical products were significantly improved.

Keywords： cefixime； anti-solvent crystallization； spherical growth； mechanism

Received 2015-04-30;

Fund:

国家自然科学基金（21376174）。

Corresponding Authors: 龚俊波,E-mail:junbo_gong@tju.edu.cn。 Email: junbo_gong@tju.edu.cn

About author: 宋晓鹏(1989-),男,硕士研究生,现从事工业和药物结晶方面的研究。

引用本文:

宋晓鹏, 屠民海, 龚俊波.头孢克肟溶析结晶过程球形生长机理探究[J]. 化学工业与工程, 2017,34(6): 57-61

Song Xiaopeng, Tu Minhai, Gong Junbo.Research on the Spherical Growth Mechanism of Cefixime During the Anti-Solvent Crystallization Process[J]. Chemcial Industry and Engineering, 2017,34(6): 57-61