Document Detail

Rapid Insight into Heating-Induced Phase Transformations in the Solid State of the Calcium Salt of Atorvastatin Using Multivariate Data Analysis.
MedLine Citation:
PMID:  23138263     Owner:  NLM     Status:  Publisher    
PURPOSE: To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin. METHODS: Multivariate curve resolution (MCR) was used to decompose a variable-temperature synchrotron X-ray powder diffraction (VT-XRPD) data matrix into diffraction patterns and concentration profiles of pure drug phases. RESULTS: By means of the MCR-estimated diffraction patterns and concentration profiles, the trihydrate phase of the drug salt was found to dehydrate sequentially into two partially dehydrated hydrate structures upon heating from 25 to 110°C, with no associated breakage of the original crystal lattice. During heating from 110 to 140°C, the remaining water was lost from the solid drug salt, which instantly collapsed into a liquid crystalline phase. An isotropic melt was formed above 155°C. Thermogravimetric analysis, hot-stage polarized light microscopy, and hot-stage Raman spectroscopy combined with principal component analysis (PCA) was shown to provide consistent results. CONCLUSIONS: This study demonstrates that MCR combined with VT-XRPD is a powerful tool for rapid interpretation of complex dehydration behavior of drug hydrates, and it is also the first report on a liquid crystalline phase of the calcium salt of atorvastatin.
Niels Peter Aae Christensen; Bernard Van Eerdenbrugh; Kaho Kwok; Lynne S Taylor; Andrew D Bond; Thomas Rades; Jukka Rantanen; Claus Cornett
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-10
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
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