In situ monitoring of polymorph transformation of clopidogrel hydrogen sulfate using measurement of ultrasonic velocity.
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.
Kim
Hye-Jin
HJ
Crystallization Process and Engineering Laboratory, Department of Chemical Engineering, Hanbat National University, San16-1, Dukmyung-dong, Yuseong, Deajeon 305-719, South Korea.
Kim
Kwang-Joo
KJ
D002152:Calorimetry, Differential Scanning; D000077144:Clopidogrel; D003460:Crystallization; D018360:Crystallography, X-Ray; D008968:Molecular Conformation; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry*; D012995:Solubility; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000737:chemistry; D014465:Ultrasonics
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine