Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol

A thorough, systematic study into the effect that structurally related impurities have on both the process and product quality during the crystallization of an active pharmaceutical ingredient is presented. The presence of acetanilide and metacetamol influences the crystallization and product qualit...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stephanie J. Urwin, Stephanie Yerdelen, Ian Houson, Joop H. ter Horst
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	industrial crystallization crystal product quality structurally related impurities impurity rejection Crystallography QD901-999
Acceso en línea:	https://doaj.org/article/6e2bee3b1df34bd7b66e944f4920ba63
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6e2bee3b1df34bd7b66e944f4920ba63
record_format	dspace
spelling	oai:doaj.org-article:6e2bee3b1df34bd7b66e944f4920ba632021-11-25T17:18:32ZImpact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol10.3390/cryst111113442073-4352https://doaj.org/article/6e2bee3b1df34bd7b66e944f4920ba632021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4352/11/11/1344https://doaj.org/toc/2073-4352A thorough, systematic study into the effect that structurally related impurities have on both the process and product quality during the crystallization of an active pharmaceutical ingredient is presented. The presence of acetanilide and metacetamol influences the crystallization and product quality of paracetamol. Where high concentrations of either impurity were present in the crystallization feed, product recovery decreased by up to 15%. Acetanilide is included in the final product through adsorption onto the particle surface in concentrations up to 0.79 mol%, which can be reduced to acceptable levels through product reslurrying. The presence of metacetamol results in much higher concentrations—up to 6.78 mol% in the final product, of which approximately 1 mol% is incorporated into the crystal lattice, resulting in the perturbation of the unit-cell dimensions. The incidental crystallization and subsequent isolation of metastable Form II paracetamol increased product purity in the presence of a low metacetamol concentration. This metastable product converts to stable paracetamol Form I through reslurrying, offering an efficient metacetamol impurity rejection route. The morphology of the product is modified consistently by both impurities. An elongation of the normal prismatic shape is observed, which in the extreme case of high metacetamol contamination results in the isolation of fine, fragile needles. This problematic morphology is also improved by a reslurrying of the crystallization product to give a more equilateral shape. This systematic study of the influence of acetanilide and metacetamol on the crystallization of paracetamol builds a well-rounded picture of the concomitant impact of impurities on the principal quality attributes of a crystallization product.Stephanie J. UrwinStephanie YerdelenIan HousonJoop H. ter HorstMDPI AGarticleindustrial crystallizationcrystal product qualitystructurally related impuritiesimpurity rejectionCrystallographyQD901-999ENCrystals, Vol 11, Iss 1344, p 1344 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	industrial crystallization crystal product quality structurally related impurities impurity rejection Crystallography QD901-999
spellingShingle	industrial crystallization crystal product quality structurally related impurities impurity rejection Crystallography QD901-999 Stephanie J. Urwin Stephanie Yerdelen Ian Houson Joop H. ter Horst Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol
description	A thorough, systematic study into the effect that structurally related impurities have on both the process and product quality during the crystallization of an active pharmaceutical ingredient is presented. The presence of acetanilide and metacetamol influences the crystallization and product quality of paracetamol. Where high concentrations of either impurity were present in the crystallization feed, product recovery decreased by up to 15%. Acetanilide is included in the final product through adsorption onto the particle surface in concentrations up to 0.79 mol%, which can be reduced to acceptable levels through product reslurrying. The presence of metacetamol results in much higher concentrations—up to 6.78 mol% in the final product, of which approximately 1 mol% is incorporated into the crystal lattice, resulting in the perturbation of the unit-cell dimensions. The incidental crystallization and subsequent isolation of metastable Form II paracetamol increased product purity in the presence of a low metacetamol concentration. This metastable product converts to stable paracetamol Form I through reslurrying, offering an efficient metacetamol impurity rejection route. The morphology of the product is modified consistently by both impurities. An elongation of the normal prismatic shape is observed, which in the extreme case of high metacetamol contamination results in the isolation of fine, fragile needles. This problematic morphology is also improved by a reslurrying of the crystallization product to give a more equilateral shape. This systematic study of the influence of acetanilide and metacetamol on the crystallization of paracetamol builds a well-rounded picture of the concomitant impact of impurities on the principal quality attributes of a crystallization product.
format	article
author	Stephanie J. Urwin Stephanie Yerdelen Ian Houson Joop H. ter Horst
author_facet	Stephanie J. Urwin Stephanie Yerdelen Ian Houson Joop H. ter Horst
author_sort	Stephanie J. Urwin
title	Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol
title_short	Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol
title_full	Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol
title_fullStr	Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol
title_full_unstemmed	Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol
title_sort	impact of impurities on crystallization and product quality: a case study with paracetamol
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6e2bee3b1df34bd7b66e944f4920ba63
work_keys_str_mv	AT stephaniejurwin impactofimpuritiesoncrystallizationandproductqualityacasestudywithparacetamol AT stephanieyerdelen impactofimpuritiesoncrystallizationandproductqualityacasestudywithparacetamol AT ianhouson impactofimpuritiesoncrystallizationandproductqualityacasestudywithparacetamol AT joophterhorst impactofimpuritiesoncrystallizationandproductqualityacasestudywithparacetamol
_version_	1718412536151277568

Impact of Impurities on Crystallization and Product Quality: A Case Study with Paracetamol

Ejemplares similares