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Journal of Chinese Pharmaceutical Sciences ›› 2015, Vol. 24 ›› Issue (1): 40-46.DOI: 10.5246/jcps.2015.01.005

• Original articles • Previous Articles     Next Articles

Centrifugation-assisted preparation and thermostability of Form I clopidogrel hydrogen sulfate

Ju Ao1, Haitao Gao2, Xiaoping Tang2, Lan Zhou1, Guoqing Zhang1*   

  1. 1. Engineering Research Center for Eco-Dyeing and Finishing of Textiles, Ministry of Education, Zhejiang Sci-Tech University, Hangzhou 310018, China
    2. Zhejiang Apeloa Medical Technology Co., Ltd., Jinhua 322118, China
  • Received:2014-06-23 Revised:2014-08-28 Online:2015-01-15 Published:2014-09-01
  • Contact: Tel.: 86-571-86843588, Fax: 86-571-86843619
  • Supported by:

    National Natural Science Foundation of China (Grant No. 51403188), Zhejiang Provincial Natural Science Foundation of China (Grant No. LY13E030004), Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20123318120005).

Abstract:

Of all reported polymorphs of clopidogrel hydrogen sulfate, Form I is difficult to produce and store owing to its poor thermostability. It is reported that Form I can spontaneously transform into Form II at high temperature and humidity. In this study, high purity Form I of clopidogrel hydrogen sulfate with good thermodynamic stability was prepared by a centrifugation-assisted recrystallization technology. The resultant product was characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscope (SEM). The results showed that the crystallinity and crystallite size of the Form I prepared by the centrifugation-assisted recrystallization method were larger than those obtained by conventional anti-solvent recrystallization methods. Long-term thermostability testing demonstrated that the improved product can keep stable crystal structure even at high temperature and humidity.

Key words: Clopidogrel hydrogen sulfate, Polymorph, Centrifugation-assisted recrystallization, Thermostability

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