Determination of composition distributions of multi-particle crystalline samples by sequential dissolution with concomitant particle sizing and solution analysis

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dc.contributor.author Moynihan, Humphrey A.
dc.contributor.author Armstrong, Declan
dc.date.accessioned 2018-07-12T13:54:07Z
dc.date.available 2018-07-12T13:54:07Z
dc.date.issued 2018-04
dc.identifier.citation Moynihan, H. A. and Armstrong, D. (2018) 'Determination of composition distributions of multi-particle crystalline samples by sequential dissolution with concomitant particle sizing and solution analysis', CrystEngComm, 20(18), pp. 2617-2633. DOI: 10.1039/C8CE00206A en
dc.identifier.volume 20 en
dc.identifier.issued 18 en
dc.identifier.startpage 2617 en
dc.identifier.endpage 2633 en
dc.identifier.issn 1466-8033
dc.identifier.uri http://hdl.handle.net/10468/6453
dc.identifier.doi 10.1039/C8CE00206A
dc.description.abstract Impurities arise in the production of molecular pharmaceutical and fine chemical products and are often addressed by crystallisation. However, impurities are not always adequately removed by crystallisations and in some cases impurities are to a certain extent incorporated within crystal particles. The present work aims to develop approaches to mapping the distribution of impurities within crystal particles for samples of multiple particles by controlled stepwise dissolution in conjunction with analysis by HPLC and sizing of the crystals. 2-Nitro-4-trifluoromethylacetanilide (1) was selected as the compound for study while 4-methyl-2-nitroacetanilide (2), 4-chloro-2-nitroacetanilide (3) and N-(2-nitro-4-trifluoromethylphenyl)pivalamide (4) were selected as the added impurities. The degree of incorporation of additives 2, 3 and 4 into crystals of compound 1 grown from solutions containing up to 10% of the additive was determined, using 50% aqueous ethanol and toluene as solvents. The stepwise dissolution of samples of crystals of compound 1 in hexane, in which compound 1 has low solubility, containing 2-(2-ethylhexyloxy)ethanol to inhibit flocculation, showed reasonably even dissolution of all crystal particles. Analysis of the resulting solutions by HPLC gave composition data which could be assigned to averaged dissolution regions of the crystals, generating distributions of the level of each additive throughout the crystal particle, these being found to be relatively even for additive 2 and 3, and uneven for additive 4. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Royal Society of Chemistry en
dc.relation.uri http://pubs.rsc.org/en/content/articlehtml/2018/ce/c8ce00206a
dc.rights © The Royal Society of Chemistry 2018. This is the Accepted Manuscript version of a published work that appeared in final form in CrystEngCommon.To access the final published version of record, see http://pubs.rsc.org/en/content/articlehtml/2018/ce/c8ce00206a en
dc.subject Pharmaceutical impurities en
dc.subject Solid solutions en
dc.subject Dissolution en
dc.title Determination of composition distributions of multi-particle crystalline samples by sequential dissolution with concomitant particle sizing and solution analysis en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Humphrey Moynihan, Chemistry, University College Cork, Cork, Ireland. +353-21-490-3000 Email: h.moynihan@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted for 12 months after publication by request of the publisher. en
dc.check.date 2019-04-16
dc.date.updated 2018-07-12T13:45:40Z
dc.description.version Accepted Version en
dc.internal.rssid 434582175
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle CrystEngComm en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress H.Moynihan@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2275/IE/Synthesis and Solid State Pharmaceutical Centre (SSPC)/ en


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