Novel biphasic lipolysis method to predict in vivo performance of lipid-based formulations

Simple item page
dc.contributor.authorO'Dwyer, Patrick J
dc.contributor.authorBox, Karl J.
dc.contributor.authorKoehl, Niklas J.
dc.contributor.authorBennett-Lenane, Harriet
dc.contributor.authorReppas, Christos
dc.contributor.authorHolm, René
dc.contributor.authorKuentz, Martin
dc.contributor.authorGriffin, Brendan T.
dc.contributor.funderHorizon 2020en
dc.date.accessioned2020-09-10T10:54:09Z
dc.date.available2020-09-10T10:54:09Z
dc.date.issued2020-08-06
dc.date.updated2020-09-08T11:08:32Z
dc.description.abstractThe absence of an intestinal absorption sink is a significant weakness of standard in vitro lipolysis methods, potentially leading to poor prediction of in vivo performance and an overestimation of drug precipitation. In addition, the majority of the described lipolysis methods only attempt to simulate intestinal conditions, thus overlooking any supersaturation or precipitation of ionizable drugs as they transition from the acidic gastric environment to the more neutral conditions of the intestine. The aim of this study was to develop a novel lipolysis method incorporating a two-stage gastric-to-intestinal transition and an absorptive compartment to reliably predict in vivo performance of lipid-based formulations (LBFs). Drug absorption was mimicked by in situ quantification of drug partitioning into a decanol layer. The method was used to characterize LBFs from four studies described in the literature, involving three model drugs (i.e., nilotinib, fenofibrate, and danazol) where in vivo bioavailability data have previously been reported. The results from the novel biphasic lipolysis method were compared to those of the standard pH-stat method in terms of reliability for predicting the in vivo performance. For three of the studies, the novel biphasic lipolysis method more reliably predicted the in vivo bioavailability compared to the standard pH-stat method. In contrast, the standard pH-stat method was found to produce more predictive results for one study involving a series of LBFs composed of the soybean oil, glyceryl monolinoleate (Maisine CC), Kolliphor EL, and ethanol. This result was surprising and could reflect that increasing concentrations of ethanol (as a cosolvent) in the formulations may have resulted in greater partitioning of the drug into the decanol absorptive compartment. In addition to the improved predictivity for most of the investigated systems, this biphasic lipolysis method also uses in situ analysis and avoids time- and resource-intensive sample analysis steps, thereby facilitating a higher throughput capacity and biorelevant approach for characterization of LBFs.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationO’Dwyer, P. J., Box, K. J., Koehl, N. J., Bennett-Lenane, H., Reppas, C., Holm, R., Kuentz, M. and Griffin, B. T. (2020) 'Novel Biphasic Lipolysis Method To Predict in Vivo Performance of Lipid-Based Formulations', Molecular Pharmaceutics, 17(9), pp. 3342-3352. doi: 10.1021/acs.molpharmaceut.0c00427en
dc.identifier.doi10.1021/acs.molpharmaceut.0c00427en
dc.identifier.endpage3352en
dc.identifier.issn1543-8392
dc.identifier.issued9en
dc.identifier.journaltitleMolecular Pharmaceuticsen
dc.identifier.startpage3342en
dc.identifier.urihttps://hdl.handle.net/10468/10503
dc.identifier.volume17en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
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.relation.urihttps://pubs.acs.org/doi/10.1021/acs.molpharmaceut.0c00427
dc.rights© 2020 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.0c00427en
dc.subjectLipolysisen
dc.subjectBiphasic dissolutionen
dc.subjectLipid-based formulationsen
dc.subjectIn vitro digestionen
dc.subjectAbsorptionen
dc.subjectIn vitro−in vivo relationship (IVIVR)en
dc.titleNovel biphasic lipolysis method to predict in vivo performance of lipid-based formulationsen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 3 of 3
Thumbnail Image
Name:
Novel_Biphasic_Lipolysis_Testing_of_LBFs_to_Predict_In_Vivo_Performance_04-08-20_Clean_version.docx
Size:
993.87 KB
Format:
Microsoft Word XML
Description:
Author's original
Thumbnail Image
Name:
Supplementary_Material_Biphasic_Lipolysis_04-08-20.docx
Size:
686.47 KB
Format:
Unknown data format
Description:
Supporting information
Download
Thumbnail Image
Name:
acs.molpharmaceut.0c00427.pdf
Size:
1.4 MB
Format:
Adobe Portable Document Format
Description:
Accepted version
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Pharmacy - Journal Articles