Amorphous solid dispersions of enzalutamide and novel polysaccharide derivatives: investigation of relationships between polymer structure and performance

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dc.contributor.authorWilson, Venecia R.en
dc.contributor.authorLou, Xiaochunen
dc.contributor.authorOsterling, Donald J.en
dc.contributor.authorStolarik, DeAnne F.en
dc.contributor.authorJenkins, Gary J.en
dc.contributor.authorNichols, Brittany L. B.en
dc.contributor.authorDong, Yifanen
dc.contributor.authorEdgar, Kevin J.en
dc.contributor.authorZhang, Geoff G. Z.en
dc.contributor.authorTaylor, Lynne S.en
dc.contributor.departmentChemistryen
dc.contributor.departmentSustainable Biomaterialsen
dc.date.accessioned2021-09-02T14:50:39Zen
dc.date.available2021-09-02T14:50:39Zen
dc.date.issued2020-10-28en
dc.date.updated2021-09-02T14:50:36Zen
dc.description.abstractAmorphous solid dispersion (ASD) is a widely employed formulation technique for drugs with poor aqueous solubility. Polymers are integral components of ASDs, but mechanisms by which polymers lead to the generation and maintenance of supersaturated solutions, which enhance oral absorption in vivo, are poorly understood. Herein, a diverse group of newly synthesized cellulose derivatives was evaluated for their ability to inhibit crystallization of enzalutamide, a poorly soluble compound used to treat prostate cancer. ASDs were prepared from selected polymers, specifically a somewhat hydrophobic polymer that was extremely effective at inhibiting drug crystallization, and a less effective, but more hydrophilic, crystallization inhibitor, that might afford better release. Drug membrane transport rate was evaluated in vitro and compared to in vivo performance, following oral dosing in rats. Good correlation was noted between the in vitro diffusion cell studies and the in vivo data. The ASD formulated with the less effective crystallization inhibitor outperformed the ASD prepared with the highly effective crystallization inhibitor in terms of the amount and rate of drug absorbed in vivo. This study provides valuable insight into key factors impacting oral absorption from enabling ASD formulations, and how best to evaluate such formulations using in vitro approaches.en
dc.description.versionPublished versionen
dc.format.extent12 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN 18535 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-020-75077-7en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidEdgar, Kevin [0000-0002-9459-9477]en
dc.identifier.other10.1038/s41598-020-75077-7 (PII)en
dc.identifier.pmid33116200en
dc.identifier.urihttp://hdl.handle.net/10919/104902en
dc.identifier.volume10en
dc.language.isoenen
dc.publisherNature Researchen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000587657600031&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectCELLULOSE OMEGA-CARBOXYESTERSen
dc.subjectWATER-SOLUBLE DRUGen
dc.subjectIN-VITROen
dc.subjectDISSOLUTION PERFORMANCEen
dc.subjectCLASSIFICATION-SYSTEMen
dc.subjectIMPACTen
dc.subjectCRYSTALLIZATIONen
dc.subjectPHARMACOKINETICSen
dc.subjectSUPERSATURATIONen
dc.subjectBIOAVAILABILITYen
dc.subject.meshAnimalsen
dc.subject.meshRatsen
dc.subject.meshRats, Sprague-Dawleyen
dc.subject.meshWateren
dc.subject.meshPhenylthiohydantoinen
dc.subject.meshPolymersen
dc.subject.meshPolysaccharidesen
dc.subject.meshDrug Delivery Systemsen
dc.subject.meshCrystallizationen
dc.subject.meshSolubilityen
dc.subject.meshMaleen
dc.subject.meshHydrophobic and Hydrophilic Interactionsen
dc.titleAmorphous solid dispersions of enzalutamide and novel polysaccharide derivatives: investigation of relationships between polymer structure and performanceen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
dcterms.dateAccepted2020-09-04en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Natural Resources & Environmenten
pubs.organisational-group/Virginia Tech/Natural Resources & Environment/Sustainable Biomaterialsen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Natural Resources & Environment/CNRE T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Durelle Scotten

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