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Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for Comparative Characterization of Complex Mixture Drugs
dc.contributor.author | Hewarathna, Asha | |
dc.contributor.author | Mozziconacci, Olivier | |
dc.contributor.author | Nariya, Maulik K. | |
dc.contributor.author | Kleindl, Peter Alan | |
dc.contributor.author | Xiong, Jian | |
dc.contributor.author | Fisher, Adam C. | |
dc.contributor.author | Joshi, Sangeeta B. | |
dc.contributor.author | Middaugh, C. Russell | |
dc.contributor.author | Forrest, M. Laird | |
dc.contributor.author | Volkin, David B. | |
dc.contributor.author | Deeds, Eric J. | |
dc.contributor.author | Schöneich, Christian | |
dc.date.accessioned | 2019-11-07T22:05:43Z | |
dc.date.available | 2019-11-07T22:05:43Z | |
dc.date.issued | 2017-11-01 | |
dc.identifier.citation | Hewarathna, A., Mozziconacci, O., Nariya, M. K., Kleindl, P. A., Xiong, J., Fisher, A. C., … Schöneich, C. (2017). Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for Comparative Characterization of Complex Mixture Drugs. Journal of pharmaceutical sciences, 106(11), 3257–3269. doi:10.1016/j.xphs.2017.06.022 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/29725 | |
dc.description | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | en_US |
dc.description.abstract | As the second of a 3-part series of articles in this issue concerning the development of a mathematical model for comparative characterization of complex mixture drugs using crofelemer (CF) as a model compound, this work focuses on the evaluation of the chemical stability profile of CF. CF is a biopolymer containing a mixture of proanthocyanidin oligomers which are primarily composed of gallocatechin with a small contribution from catechin. CF extracted from drug product was subjected to molecular weight–based fractionation and thiolysis. Temperature stress and metal-catalyzed oxidation were selected for accelerated and forced degradation studies. Stressed CF samples were size fractionated, thiolyzed, and analyzed with a combination of negative-ion electrospray ionization mass spectrometry (ESI-MS) and reversed-phase-HPLC with UV absorption and fluorescence detection. We further analyzed the chemical stability data sets for various CF samples generated from reversed-phase-HPLC-UV and ESI-MS using data-mining and machine learning approaches. In particular, calculations based on mutual information of over 800,000 data points in the ESI-MS analytical data set revealed specific CF cleavage and degradation products that were differentially generated under specific storage/degradation conditions, which were not initially identified using traditional analysis of the ESI-MS results. | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved. This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | en_US |
dc.subject | Crofelemer | en_US |
dc.subject | Complex mixture | en_US |
dc.subject | Chemical stability | en_US |
dc.subject | Oxidation | en_US |
dc.subject | Mass spectrometry | en_US |
dc.subject | HPLC | en_US |
dc.subject | Mutual information scores | en_US |
dc.subject | Machine learning | en_US |
dc.title | Chemical Stability of the Botanical Drug Substance Crofelemer: A Model System for Comparative Characterization of Complex Mixture Drugs | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Hewarathna, Asha | |
kusw.kuauthor | Mozziconacci, Olivier | |
kusw.kuauthor | Nariya, Maulik K. | |
kusw.kuauthor | Kleindl, Peter Alan | |
kusw.kuauthor | Xiong, Jian | |
kusw.kuauthor | Joshi, Sangeeta B. | |
kusw.kuauthor | Middaugh, C. Russell | |
kusw.kuauthor | Forrest, M. Laird | |
kusw.kuauthor | Volkin, David B. | |
kusw.kuauthor | Deeds, Eric J. | |
kusw.kuauthor | Schöneich, Christian | |
kusw.kudepartment | Pharmaceutical Chemistry | en_US |
kusw.kudepartment | Physics and Astronomy | en_US |
dc.identifier.doi | 10.1016/j.xphs.2017.06.022 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC6644711 | en_US |
dc.rights.accessrights | openAccess | en_US |