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 - 2012/10
Y1 - 2012/10
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
SN - 0939-6411
VL - 82
SP - 410
EP - 416
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
IS - 2
ER -