Impurity occurrence and removal in crystalline products from process reactions

Moynihan, Humphrey A.; Horgan, Danielle E.

Impurity occurrence and removal in crystalline products from process reactions

dc.contributor.author	Moynihan, Humphrey A.
dc.contributor.author	Horgan, Danielle E.
dc.contributor.funder	Irish Research Council	en
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	University College Cork	en
dc.contributor.funder	Clarochem Ireland Ltd
dc.date.accessioned	2017-11-10T11:42:03Z
dc.date.available	2017-11-10T11:42:03Z
dc.date.issued	2017-04-10
dc.date.updated	2017-11-06T09:38:08Z
dc.description.abstract	The behavior of impurities when subjected to crystallizations, and related processes such as recrystallization and reslurrying, has been reviewed with a particular focus on the years 2000–2015, but also including significant cases from outside that period. Small molecule pharmaceuticals and similar small organic molecules are included but not biomolecules, inorganics, or minerals. Phase impurities are only covered when a phase transformation is involved with the management of an impurity. Introductory examples illustrating some general features of crystallization as a method of purification are presented, as well as approaches to quantifying the effectiveness of purification. The review classifies cases based on the behavior of the specific impurities covered. The classes of behavior observed are the removal by washing, recrystallization, or reslurrying (Class I), impurities not being removed by these operations (Class II), and impurities which are removed in conjunction with a phase transformation (Class III). Examples of each of these types of behavior are presented, with many processes producing impurities which fall into more than one of these classes. Studies on the inclusion of extraneous molecules into crystalline materials are also covered. These particularly include the incorporation of compounds as solid solutions, but also eutectic formation and inclusion at surfaces during crystal growth. The relationship between types of impurities and behavior during processing is also examined.	en
dc.description.sponsorship	Irish Research Council (IRSCET-Clarochem-2010-02); University College Cork (2013 Strategic Research Fund); Science Foundation Ireland (Grant Number 05/PICA/B802/EC07)	en
dc.description.status	Peer reviewed	en
dc.description.version	Accepted Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Moynihan, H. A. and Horgan, D. E. (2017) 'Impurity occurrence and removal in crystalline products from process reactions', Organic Process Research and Development, 21(5), pp. 689-704. doi:10.1021/acs.oprd.6b00403	en
dc.identifier.doi	10.1021/acs.oprd.6b00403
dc.identifier.endpage	704	en
dc.identifier.issn	1083-6160
dc.identifier.issued	5	en
dc.identifier.journaltitle	Organic Process Research and Development	en
dc.identifier.startpage	689	en
dc.identifier.uri	https://hdl.handle.net/10468/5006
dc.identifier.volume	21	en
dc.language.iso	en	en
dc.publisher	American Chemical Society	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Strategic Research Cluster/07/SRC/B1158/IE/SRC SSPS: Solid State Pharmaceuticals Cluster (SSPC)/	en
dc.relation.project	info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/	en
dc.rights	© 2017, American Chemical Society. All rights reserved. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Organic Process Research and Development, after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/acs.oprd.6b00403	en
dc.subject	Pharmaceuticals	en
dc.subject	Impurities	en
dc.subject	Crystallisation	en
dc.subject	Solid solutions	en
dc.title	Impurity occurrence and removal in crystalline products from process reactions	en
dc.type	Article (peer-reviewed)	en