NDLI: Rapid Insight into Heating-Induced Phase Transformations in the Solid State of the Calcium Salt of Atorvastatin Using Multivariate Data Analysis

Content Provider	Springer Nature Link
Author	Christensen, Niels Peter Aae Van Eerdenbrugh, Bernard Kwok, Kaho Taylor, Lynne S. Bond, Andrew D. Rades, Thomas Rantanen, Jukka Cornett, Claus
Copyright Year	2012
Abstract	To investigate the heating-induced dehydration and melting behavior of the trihydrate phase of the calcium salt of atorvastatin.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.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.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.
Starting Page	826
Ending Page	835
Page Count	10
File Format	PDF
ISSN	07248741
Journal	Pharmaceutical Research
Volume Number	30
Issue Number	3
e-ISSN	1573904X
Language	English
Publisher	Springer US
Publisher Date	2012-11-10
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Pharmacology/Toxicology Pharmacy Biochemistry Medical Law Biomedical Engineering
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Pharmacology Molecular Medicine Pharmacology (medical) Biotechnology Pharmaceutical Science

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