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An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders

Accurate quantification of impurities existing as separate crystalline phases at trace levels in drug materials is an important issue in the pharmaceutical industry. In the present study, a thermoanalytical approach previously developed for quantifying trace levels of polymorphic impurity (form II m...

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Autores principales: Tong, Henry H.Y., Shekunov, Boris Y., Chan, John P., Mok, Cedric K.F., Hung, Henry C.M., Chow, Albert H.L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125510/
https://www.ncbi.nlm.nih.gov/pubmed/15848004
http://dx.doi.org/10.1016/j.ijpharm.2005.02.024
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author Tong, Henry H.Y.
Shekunov, Boris Y.
Chan, John P.
Mok, Cedric K.F.
Hung, Henry C.M.
Chow, Albert H.L.
author_facet Tong, Henry H.Y.
Shekunov, Boris Y.
Chan, John P.
Mok, Cedric K.F.
Hung, Henry C.M.
Chow, Albert H.L.
author_sort Tong, Henry H.Y.
collection PubMed
description Accurate quantification of impurities existing as separate crystalline phases at trace levels in drug materials is an important issue in the pharmaceutical industry. In the present study, a thermoanalytical approach previously developed for quantifying trace levels of polymorphic impurity (form II metastable nuclei) in commercial salmeterol xinafoate powders has been successfully applied with slight modifications to ribavirin, an antiviral drug exhibiting roughly similar polymorph-dependent crystallization kinetics in melts to that of salmeterol xinafoate. Essentially, the approach involved modeling of the crystallization kinetics of both tested and reference drug materials in melts using the Avrami-Erofe’ev (AE) rate expression, derivation of a mathematical equation for relating the AE kinetic constant to the composition of reference polymorph mixtures, and the use of this derived equation (in the form of a calibration curve) to calculate the impurity contents of the tested samples from their computed AE constants. For ribavirin, modification of the latter equation by incorporation of an empirical exponent was found necessary to account for the composition-dependent changes in crystallization kinetics of the reference mixtures. Such modification has made possible the determination of polymorphic impurity content of as low as 0.004% (w/w) in ribavirin samples induced by different forms of grinding treatment.
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spelling pubmed-71255102020-04-08 An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders Tong, Henry H.Y. Shekunov, Boris Y. Chan, John P. Mok, Cedric K.F. Hung, Henry C.M. Chow, Albert H.L. Int J Pharm Article Accurate quantification of impurities existing as separate crystalline phases at trace levels in drug materials is an important issue in the pharmaceutical industry. In the present study, a thermoanalytical approach previously developed for quantifying trace levels of polymorphic impurity (form II metastable nuclei) in commercial salmeterol xinafoate powders has been successfully applied with slight modifications to ribavirin, an antiviral drug exhibiting roughly similar polymorph-dependent crystallization kinetics in melts to that of salmeterol xinafoate. Essentially, the approach involved modeling of the crystallization kinetics of both tested and reference drug materials in melts using the Avrami-Erofe’ev (AE) rate expression, derivation of a mathematical equation for relating the AE kinetic constant to the composition of reference polymorph mixtures, and the use of this derived equation (in the form of a calibration curve) to calculate the impurity contents of the tested samples from their computed AE constants. For ribavirin, modification of the latter equation by incorporation of an empirical exponent was found necessary to account for the composition-dependent changes in crystallization kinetics of the reference mixtures. Such modification has made possible the determination of polymorphic impurity content of as low as 0.004% (w/w) in ribavirin samples induced by different forms of grinding treatment. Elsevier B.V. 2005-05-13 2005-04-07 /pmc/articles/PMC7125510/ /pubmed/15848004 http://dx.doi.org/10.1016/j.ijpharm.2005.02.024 Text en Copyright © 2005 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Tong, Henry H.Y.
Shekunov, Boris Y.
Chan, John P.
Mok, Cedric K.F.
Hung, Henry C.M.
Chow, Albert H.L.
An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders
title An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders
title_full An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders
title_fullStr An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders
title_full_unstemmed An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders
title_short An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders
title_sort improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7125510/
https://www.ncbi.nlm.nih.gov/pubmed/15848004
http://dx.doi.org/10.1016/j.ijpharm.2005.02.024
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