In situ monitoring of polymorph transformation of clopidogrel hydrogen sulfate using measurement of ultrasonic velocity

被引：16
|
作者：
Kim, Hye-Jin [1 ]
Kim, Kwang-Joo [1 ]
机构：
[1] Hanbat Natl Univ, Crystallizat Proc & Engn Lab, Dept Chem Engn, Taejon 305719, South Korea
来源：
JOURNAL OF PHARMACEUTICAL SCIENCES | 2008年 / 97卷 / 10期
关键词：
crystallization; polymorphism; processing; crystal engineering; crystals;
D O I：
10.1002/jps.21313
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Transformation of polymorph I of clopidogrel hydrogen sulfate (CHS) to polymorph II of CHS during the crystallization was monitored by using in situ measurement of ultrasonic velocity. Drowning-out crystallization using methanol as a solvent and isopropyl alcohol as nonsolvent was carried out. The polymorphs were identified with X-ray powder diffraction analysis. From the in situ measurement of the ultrasonic velocity, induction time for Forms I and II, width for growth of Form I, width for transformation from Forms I to II were measured in-line processing. Influence of temperature and methanol/isopropyl alcohol ratio on change of polymorph was analyzed by measurement of ultrasonic velocity. As a result, transformation of polymorph was successfully monitored by ultrasonic velocity in-line process. (C) 2008 Wiley-Liss, Inc.
引用
收藏
页码：4473 / 4484
页数：12
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