Add time:08/11/2019 Source:sciencedirect.com
ABSTRACTTransformation of polymorph I of Clopidogrel hydrogen sulfate (cas 135046-48-9) (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. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4473–4484, 2008
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