Gastrointestinal diseases and their impact on drug solubility: Celiac disease

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dc.contributor.authorEffinger, Angela
dc.contributor.authorO'Driscoll, Caitriona M.
dc.contributor.authorMcAllister, Mark
dc.contributor.authorFotaki, Nikoletta
dc.contributor.funderHorizon 2020en
dc.date.accessioned2022-02-16T09:47:31Z
dc.date.available2022-02-16T09:47:31Z
dc.date.issued2020-07-11
dc.date.updated2022-02-16T09:42:02Z
dc.description.abstractThe aim of this study was to develop an in vitro tool for predicting drug solubility and dissolution in intestinal fluids of patients with Celiac disease (CED). Biorelevant media for patients with CED were developed based on published information and a Design of Experiment (DoE) approach. The CED biorelevant media were characterised according to their surface tension, osmolality, dynamic viscosity and buffer capacity. By performing solubility studies of six drugs with different physicochemical properties in CED media, we aimed to identify drugs at high risk of altered luminal solubility in CED patients. Identified differences in CED patients compared to healthy subjects were related to a higher concentration of bile salts, lecithin and cholesterol and included as factors in the DoE resulting in 8 CED biorelevant media. Differences in media properties were observed for the surface tension between biorelevant media based on CED patients and healthy subjects. In terms of solubility, only a minimal effect of CED on the solubility of the hydrophilic neutral compound azathioprine was observed. For neutral moderately lipophilic compounds (budesonide, celecoxib), a higher surfactant concentration resulted in most cases in a higher drug solubility, while it was specific to each drug whether this was mainly driven by bile salts or lecithin. In comparison, drug solubilisation of ionisable compounds with moderate to high lipophilicity was less impacted by CED differences. The developed biorelevant CED media serve as in vitro tool to identify the main media factors impacting on drug solubility.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid105460en
dc.identifier.citationEffinger, A., O'Driscoll, C. M., McAllister, M. and Fotaki, N. (2020) 'Gastrointestinal diseases and their impact on drug solubility: Celiac disease', European Journal of Pharmaceutical Sciences, 152, 105460 (9pp). doi: 10.1016/j.ejps.2020.105460en
dc.identifier.doi10.1016/j.ejps.2020.105460en
dc.identifier.eissn1520-6017
dc.identifier.endpage9en
dc.identifier.issn0928-0987
dc.identifier.journaltitleEuropean Journal of Pharmaceutical Sciencesen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/12572
dc.identifier.volume152en
dc.language.isoenen
dc.publisherElsevier B.V.en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-ITN-ETN/674909/EU/Pharmaceutical Education And Research with Regulatory Links: Innovative drug development strategies and regulatory tools tailored to facilitate earlier access to medicines/PEARRLen
dc.rights© 2020, Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.en
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectBiorelevant mediaen
dc.subjectCeliac diseaseen
dc.subjectGastrointestinal diseasesen
dc.subjectPhysicochemical propertiesen
dc.subjectSolubilityen
dc.titleGastrointestinal diseases and their impact on drug solubility: Celiac diseaseen
dc.typeArticle (peer-reviewed)en
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