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 tem...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.展开更多
基金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)
文摘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.
