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dc.contributor.authorPrice, Daniel J.
dc.contributor.authorKuentz, Martin
dc.date.accessioned2020-03-03T09:24:50Z
dc.date.available2020-03-03T09:24:50Z
dc.date.issued2020-01
dc.identifier.doi10.1016/j.ejps.2019.105113
dc.identifier.urihttps://irf.fhnw.ch/handle/11654/30661
dc.description.abstractMesoporous silica has emerged as an enabling formulation for poorly soluble active pharmaceutical ingredients (APIs). Unlike other formulations, mesoporous silica typically does not inhibit precipitation of supersaturated API therefore, a suitable precipitation inhibitor (PI) should be added to increase absorption from the gastrointestinal (GI) tract. However, there is limited research about optimal processes for combining PIs with silica formulations. Typically, the PI is added by simply blending the API-loaded silica mechanically with the selected PI. This has the drawback of an additional blending step and may also not be optimal with regard to release of drug and PI. By contrast, loading PI simultaneously with the API onto mesoporous silica, i.e. co-incorporation, is attractive from both a performance and practical perspective. The aim of this study was to demonstrate the utility of a co-incorporation approach for combining PIs with silica formulations, and to develop a mechanistic rationale for improvement of the performance of silica formulations using the co-incorporation approach. The results indicate that co-incorporating HPMCAS with glibenclamide onto silica significantly improved the extent and duration of drug supersaturation in single-medium and transfer dissolution experiments. Extensive spectroscopic characterization of the formulation revealed that the improved performance was related to the formation of drug-polymer interactions already in the solid state; the immobilization of API-loaded silica on HPMCAS plates, which prevents premature release and precipitation of API; and drug-polymer proximity on disintegration of the formulation, allowing for rapid onset of precipitation inhibition. The data suggests that co-incorporating the PI with the API is appealing for silica formulations from both a practical and formulation performance perspective.en_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pubmed/31655207en_US
dc.language.isoenen_US
dc.relation.ispartofEuropean Journal of Pharmaceutical Sciencesen_US
dc.accessRightsAnonymous*
dc.subjectMechanisticen_US
dc.subjectMesoporous silicaen_US
dc.subjectPrecipitation inhibitionen_US
dc.subjectSolid dispersionen_US
dc.subjectSupersaturationen_US
dc.titleIncorporation of HPMCAS during loading of glibenclamide onto mesoporous silica improves dissolution and inhibits precipitation.en_US
dc.type01 - Zeitschriftenartikel, Journalartikel oder Magazin*
dc.audienceScienceen_US
fhnw.publicationStatePublisheden_US
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publicationen_US
fhnw.InventedHereYesen_US
fhnw.PublishedSwitzerlandYesen_US
fhnw.IsStudentsWorknoen_US
fhnw.publicationOnlineJaen_US


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