Gastrointestinal diseases and their impact on drug solubility: Crohn's 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.accessioned2022-02-16T09:58:11Z
dc.date.available2022-02-16T09:58:11Z
dc.date.issued2020-07-11
dc.date.updated2022-02-16T09:51:47Z
dc.description.abstractIn order to investigate differences in drug solubilisation and dissolution in luminal fluids of Crohn's disease (CD) patients and healthy subjects, biorelevant media representative of CD patients were developed using information from literature and a Design of Experiment (DoE) approach. The CD media were characterised in terms of surface tension, osmolality, dynamic viscosity and buffer capacity and compared to healthy biorelevant media. To identify which drug characteristics are likely to present a high risk of altered drug solubility in CD, the solubility of six drugs was assessed in CD media and solubility differences were related to drug properties. Identified differences in CD patients compared to healthy subjects were a reduced concentration of bile salts, a higher gastric pH and a higher colonic osmolality. Differences in the properties of CD compared to healthy biorelevant media were mainly observed for surface tension and osmolality. Drug solubility of ionisable compounds was altered in gastric CD media compared to healthy biorelevant media. For drugs with moderate to high lipophilicity, a high risk of altered drug solubilisation in CD is expected, since a significant negative effect of log P and a positive effect of bile salts on drug solubility in colonic and fasted state intestinal CD media was observed. Simulating the conditions in CD patients in vitro offers the possibility to identify relevant differences in drug solubilisation without conducting expensive clinical trials.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid105459en
dc.identifier.citationEffinger, A., O'Driscoll, C. M., McAllister, M. and Fotaki, N. (2020) 'Gastrointestinal diseases and their impact on drug solubility: Crohn's disease', European Journal of Pharmaceutical Sciences, 152, 105459 (13pp). doi: 10.1016/j.ejps.2020.105459en
dc.identifier.doi10.1016/j.ejps.2020.105459en
dc.identifier.eissn1520-6017
dc.identifier.endpage13en
dc.identifier.issn0928-0987
dc.identifier.journaltitleEuropean Journal of Pharmaceutical Sciencesen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/12573
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/
dc.subjectBiorelevant mediaen
dc.subjectCrohn's diseaseen
dc.subjectGastrointestinal diseasesen
dc.subjectInflammatory bowel diseaseen
dc.subjectPhysicochemical propertiesen
dc.subjectSolubilityen
dc.subject~Pharmacy - Journal Articles~en
dc.titleGastrointestinal diseases and their impact on drug solubility: Crohn's diseaseen
dc.typeArticle (peer-reviewed)en
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