dc.contributor.author	Moynihan, Humphrey A.
dc.contributor.author	Armstrong, Declan
dc.contributor.funder	Science Foundation Ireland	en
dc.date.accessioned	2019-08-08T08:25:33Z
dc.date.available	2019-08-08T08:25:33Z
dc.date.issued	2019-07
dc.date.updated	2019-08-07T11:29:04Z
dc.description.abstract	Crystallisations are widely used in pharmaceutical and fine chemical manufacturing to control impurity levels, however crystallisations do not always reduce impurities to acceptable levels. Information on the location and distribution of impurities in crystallised materials would be helpful in such cases. A two phase dissolution medium featuring a fluorocarbon non-solvent vehicle and a aqueous ethanol solvent phase has been used to determine the composition of multi-particle crystalline samples through a partial dissolution approach combined with particle sizing and HPLC analysis. 4-Chloro-2-nitroacetanilide (1) was chosen as the host compound for this study, with 4-methyl-2-nitroacetanilide (2) and 4-tert-butyl-2-nitroacetanilide (3) chosen as the guest impurities that were added to supersaturated toluene solutions of 1 at levels up to 5 mol%. The crystals that formed were subjected to a series of partial dissolution steps carried out using the biphasic dissolution medium composed of a 50% aqueous ethanol solvent phase and a perfluorohexane continuous phase. To inhibit particle agglomeration, the mixture also contained 13,13,14,14,15,15,16,16,17,17,18,18-dodecafluoro-2,5,8,11-tetraoxaoctadecane (4) as a non-ionic surfactant. The partial dissolution steps showed a relatively even dissolution with each sequential step as determined from particle sizing. Analysis of the solutions by HPLC from each partial dissolution step allowed the level of impurity to be determined, and when combined with the particle sizing data this allowed an impurity distribution to be generated. Impurity 2 was found to be relatively evenly distributed while impurity 3 was localised on or near the surfaces of crystals.	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.citation	Moynihan H. A. and Armstrong, D. (2019) 'Stepwise dissolution and composition determination of samples of multiple crystals using a dissolution medium containing aqueous alcohol and fluorocarbon phases'. RSC Advances, 9 (37), pp. 21405-21417. DOI: 10.1039/C9RA02781E	en
dc.identifier.doi	10.1039/c9ra02781e	en
dc.identifier.endpage	21417	en
dc.identifier.issn	2046-2069
dc.identifier.issued	37	en
dc.identifier.journaltitle	RSC Advances	en
dc.identifier.startpage	21405	en
dc.identifier.uri	https://hdl.handle.net/10468/8295
dc.identifier.volume	9	en
dc.language.iso	en	en
dc.publisher	Royal Society of Chemistry	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.relation.uri	https://pubs.rsc.org/en/content/articlelanding/2019/RA/C9RA02781E#!divAbstract
dc.rights	© 2018 The Authors.This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.	en
dc.rights.uri	http://creativecommons.org/licenses/by-nc/3.0/	en
dc.subject	Crystallisation	en
dc.subject	Dissolution media	en
dc.subject	Impurities	en
dc.title	Stepwise dissolution and composition determination of samples of multiple crystals using a dissolution medium containing aqueous alcohol and fluorocarbon phases	en
dc.type	Article (peer-reviewed)	en

Stepwise dissolution and composition determination of samples of multiple crystals using a dissolution medium containing aqueous alcohol and fluorocarbon phases

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