Establishing experimental parameters for biphasic transfer in vitro lipolysis model

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dc.contributor.authorKirschbaum, Hannah S.
dc.contributor.authorJede, Christian
dc.contributor.authorKoehl, Laura J.
dc.contributor.authorKuentz, Martin
dc.contributor.authorHolm, René
dc.contributor.authorGriffin, Brendan T.
dc.contributor.authorBlechar, Johannes A.
dc.contributor.authorÓDwyer, Patrick J.
dc.date.accessioned2026-10-13T13:54:01Z
dc.date.available2026-10-13T13:54:01Z
dc.date.issued2026-07-10
dc.description.abstractLipid-based–formulations (LBFs) are widely used to improve oral bioavailability of poorly water–soluble drugs. Despite their widespread use in predicting formulation performance, standard in vitro lipolysis assays often lack an absorptive sink and fail to capture the transition from gastric to intestinal environments, thereby reducing their predictive relevance for in vivo outcomes. The aim of this study was to develop a biphasic in vitro lipolysis model incorporating an absorptive sink. This might offer the potential to increase the predictive power of in vitro digestion models in the future. In this model, the absorptive sink was provided by a decanol layer, and to simulate gastrointestinal transit, two dynamic pH–transition approaches were employed: a biphasic GI–transfer model and a biphasic pH–shift model. Using nilotinib–loaded LBFs, the study established conditions for this biphasic system and examined how media composition and lipase source influence drug concentrations during formulation dispersion, digestion, and partitioning into the organic sink. The results showed that digestion experiments conducted with either porcine pancreatin or Palatase® 20000 L increased the concentration of nilotinib in the aqueous digestion medium, which correspondingly reduced partitioning of the drug into the decanol layer. For the readily dispersible Type III LBF in the biphasic GI–transfer setup, nilotinib permeation into the decanol layer decreased compared with a lipid–free control, likely due to improved drug solubilization in the aqueous digestion phase. In contrast, the poorly dispersible Type I LBF was better suited to the biphasic pH–shift setup, but it showed higher drug levels in the decanol layer, reflecting rapid partitioning of lipids—and associated crystalline drug—into the organic phase. Overall, this study establishes suitable conditions for evaluating the lipolysis of LBFs during a dynamic pH transition in the presence of an absorptive sink. This advanced approach provides additional insight to explore digestion–mediated and/or pH–mediated supersaturation during digestion of LBFs.en
dc.description.versionPublished Version
dc.format.extent12
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid127051
dc.identifier.authororcidKirschbaum, Hannah S.
dc.identifier.authororcidJede, Christian
dc.identifier.authororcidKoehl, Laura J.
dc.identifier.authororcidKuentz, Martin
dc.identifier.authororcidHolm, René
dc.identifier.authororcidGriffin, Brendan T.§0000-0001-5433-8398
dc.identifier.authororcidBlechar, Johannes A.
dc.identifier.authororcidÓDwyer, Patrick J.
dc.identifier.citationKirschbaum, H S, Jede, C, Koehl, L J, Kuentz, M, Holm, R, Griffin, B T, Blechar, J A & ÓDwyer, P J 2026, 'Establishing experimental parameters for biphasic transfer in vitro lipolysis model', International Journal of Pharmaceutics, vol. 700, 127051, pp. 1-12. https://doi.org/10.1016/j.ijpharm.2026.127051
dc.identifier.doi10.1016/j.ijpharm.2026.127051
dc.identifier.endpage12
dc.identifier.issn0378-5173
dc.identifier.journaltitleInternational Journal of Pharmaceutics
dc.identifier.startpage1
dc.identifier.urihttps://hdl.handle.net/10468/19437
dc.identifier.volume700
dc.language.isoen
dc.publisherElsevier B.V.
dc.relation.urihttps://www.scopus.com/pages/publications/105041786764
dc.rights© 2026, authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
dc.rights.accessrightsopen access
dc.rights.licensenameAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.statusPeer reviewed
dc.subjectAbsorption
dc.subjectBiphasic lipolysis
dc.subjectGastrointestinal transfer
dc.subjectIn vitro digestion
dc.subjectLipid-based formulations
dc.subjectSupersaturation
dc.subject[Pharmacy]
dc.titleEstablishing experimental parameters for biphasic transfer in vitro lipolysis modelen
dc.typeArticle (peer-reviewed)
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