Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients

Research output: Contribution to journalJournal articleResearchpeer-review

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Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients. / Christensen, Niels Peter Aae; Rantanen, Jukka; Cornett, Claus; Taylor, Lynne S.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 82, No. 2, 2012, p. 410-6.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Christensen, NPA, Rantanen, J, Cornett, C & Taylor, LS 2012, 'Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients', European Journal of Pharmaceutics and Biopharmaceutics, vol. 82, no. 2, pp. 410-6. https://doi.org/10.1016/j.ejpb.2012.07.003

APA

Christensen, N. P. A., Rantanen, J., Cornett, C., & Taylor, L. S. (2012). Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients. European Journal of Pharmaceutics and Biopharmaceutics, 82(2), 410-6. https://doi.org/10.1016/j.ejpb.2012.07.003

Vancouver

Christensen NPA, Rantanen J, Cornett C, Taylor LS. Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients. European Journal of Pharmaceutics and Biopharmaceutics. 2012;82(2):410-6. https://doi.org/10.1016/j.ejpb.2012.07.003

Author

Christensen, Niels Peter Aae ; Rantanen, Jukka ; Cornett, Claus ; Taylor, Lynne S. / Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients. In: European Journal of Pharmaceutics and Biopharmaceutics. 2012 ; Vol. 82, No. 2. pp. 410-6.

Bibtex

@article{a9a3df91b721412c83fa5c6e1df1b646,
title = "Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients",
abstract = "The aim of the present study was to combine vibrational spectroscopy and chemometrics for investigating excipient-induced disproportionation of the calcium salt of atorvastatin into the corresponding free acid form in environments relevant to manufacturing and storage of solid dosage formulations. Of the excipients investigated, citric acid and polyacrylic acid were found to induce disproportionation. Moreover, it was also observed that exposure to high relative humidity, elevated temperatures, and milling all promoted disproportionation. The results suggest that disproportionation of drug salts in powders happens via a solution-mediated mechanism and that the choice of excipient has a considerable impact on the extent of disproportionation observed. Thus, careful attention must be paid to excipient selection during pharmaceutical development and exposure to stresses such as high humidity and mechanical activation should be minimized.",
author = "Christensen, {Niels Peter Aae} and Jukka Rantanen and Claus Cornett and Taylor, {Lynne S}",
note = "Copyright {\circledC} 2012 Elsevier B.V. All rights reserved.",
year = "2012",
doi = "10.1016/j.ejpb.2012.07.003",
language = "English",
volume = "82",
pages = "410--6",
journal = "European Journal of Pharmaceutics and Biopharmaceutics",
issn = "0939-6411",
publisher = "Elsevier",
number = "2",

}

RIS

TY - JOUR

T1 - Disproportionation of the calcium salt of atorvastatin in the presence of acidic excipients

AU - Christensen, Niels Peter Aae

AU - Rantanen, Jukka

AU - Cornett, Claus

AU - Taylor, Lynne S

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2012

Y1 - 2012

N2 - The aim of the present study was to combine vibrational spectroscopy and chemometrics for investigating excipient-induced disproportionation of the calcium salt of atorvastatin into the corresponding free acid form in environments relevant to manufacturing and storage of solid dosage formulations. Of the excipients investigated, citric acid and polyacrylic acid were found to induce disproportionation. Moreover, it was also observed that exposure to high relative humidity, elevated temperatures, and milling all promoted disproportionation. The results suggest that disproportionation of drug salts in powders happens via a solution-mediated mechanism and that the choice of excipient has a considerable impact on the extent of disproportionation observed. Thus, careful attention must be paid to excipient selection during pharmaceutical development and exposure to stresses such as high humidity and mechanical activation should be minimized.

AB - The aim of the present study was to combine vibrational spectroscopy and chemometrics for investigating excipient-induced disproportionation of the calcium salt of atorvastatin into the corresponding free acid form in environments relevant to manufacturing and storage of solid dosage formulations. Of the excipients investigated, citric acid and polyacrylic acid were found to induce disproportionation. Moreover, it was also observed that exposure to high relative humidity, elevated temperatures, and milling all promoted disproportionation. The results suggest that disproportionation of drug salts in powders happens via a solution-mediated mechanism and that the choice of excipient has a considerable impact on the extent of disproportionation observed. Thus, careful attention must be paid to excipient selection during pharmaceutical development and exposure to stresses such as high humidity and mechanical activation should be minimized.

U2 - 10.1016/j.ejpb.2012.07.003

DO - 10.1016/j.ejpb.2012.07.003

M3 - Journal article

C2 - 22824098

VL - 82

SP - 410

EP - 416

JO - European Journal of Pharmaceutics and Biopharmaceutics

JF - European Journal of Pharmaceutics and Biopharmaceutics

SN - 0939-6411

IS - 2

ER -

ID: 43968663