Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis

Niels Peter Aae Christensen; Bernard Van Eerdenbrugh; Kaho Kwok; Lynne S. Taylor; Andrew Bond; Thomas Rades; Jukka Rantanen; Claus Cornett

doi:10.1007/s11095-012-0923-1

Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis

Niels Peter Aae Christensen, Bernard Van Eerdenbrugh, Kaho Kwok, Lynne S. Taylor, Andrew Bond, Thomas Rades, Jukka Rantanen, Claus Cornett

15 Citations (Scopus)

Abstract

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.

Original language	English
Journal	Pharmaceutical Research
Volume	30
Issue number	3
Pages (from-to)	826-35
Number of pages	10
ISSN	0724-8741
DOIs	https://doi.org/10.1007/s11095-012-0923-1
Publication status	Published - Mar 2013

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Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis. / Christensen, Niels Peter Aae; Van Eerdenbrugh, Bernard; Kwok, Kaho et al.
In: Pharmaceutical Research, Vol. 30, No. 3, 03.2013, p. 826-35.

Research output: Contribution to journal › Journal article › Research › peer-review

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title = "Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis",

abstract = "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.",

author = "Christensen, {Niels Peter Aae} and {Van Eerdenbrugh}, Bernard and Kaho Kwok and Taylor, {Lynne S.} and Andrew Bond and Thomas Rades and Jukka Rantanen and Claus Cornett",

year = "2013",

month = mar,

doi = "10.1007/s11095-012-0923-1",

language = "English",

volume = "30",

pages = "826--35",

journal = "Pharmaceutical Research",

issn = "0724-8741",

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T1 - Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis

AU - Christensen, Niels Peter Aae

AU - Van Eerdenbrugh, Bernard

AU - Kwok, Kaho

AU - Taylor, Lynne S.

AU - Bond, Andrew

AU - Rades, Thomas

AU - Rantanen, Jukka

AU - Cornett, Claus

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

U2 - 10.1007/s11095-012-0923-1

DO - 10.1007/s11095-012-0923-1

M3 - Journal article

C2 - 23138263

SN - 0724-8741

VL - 30

SP - 826

EP - 835

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 3

ER -

Rapid insight into heating-induced phase transformations in the solid state of the calcium salt of atorvastatin using multivariate data analysis

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