Toward simplified oral lipid-based drug delivery using mono-/di-glycerides as single component excipients

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dc.check.date2021-11-09
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorIlie, Alexandra-Roxana
dc.contributor.authorGriffin, Brendan T.
dc.contributor.authorVertzoni, Maria
dc.contributor.authorKuentz, Martin
dc.contributor.authorCuyckens, Filip
dc.contributor.authorWuyts, Koen
dc.contributor.authorKolakovic, Ruzica
dc.contributor.authorHolm, René
dc.contributor.funderHorizon 2020en
dc.date.accessioned2020-12-03T13:31:02Z
dc.date.available2020-12-03T13:31:02Z
dc.date.issued2020-11-09
dc.date.updated2020-12-03T13:13:46Z
dc.description.abstractObjective: This study aimed to systematically explore compositional effects for a series of lipid systems, on the in vitro drug solubilization and in vivo bioavailability of three poorly water-soluble drugs with different physico-chemical properties. Significance: While many lipid-based drug products have successfully reached the market, there is still a level of uncertainty on the design guidelines for such drug products with limited understanding on the influence of composition on in vitro and in vivo performance. Methods and Results: Lipid-based drug delivery systems were prepared using either single excipient systems based on partially digested triglycerides (i.e. mono- and/or di-glycerides) or increasingly complex systems by incorporating surfactants and/or triglycerides. These lipid systems were evaluated for both in vitro and in vivo behavior. Results indicated that simple single component long chain lipid systems are more beneficial for the absorption of the weak acid celecoxib and the weak base cinnarizine compared to equivalent single component medium chain lipid systems. Similarly, a two-component system produced by incorporating small amount of hydrophilic surfactant yields similar overall pharmacokinetic effects. The lipid drug delivery systems based on medium chain lipid excipients improved the in vivo exposure of the neutral drug JNJ-2A. The higher in vivo bioavailability of long chain lipid systems compared to medium chain lipid systems was in agreement with in vitro dilution and dispersion studies for celecoxib and cinnarizine. Conclusions: The present study demonstrated the benefits of using mono-/di-glycerides as single component excipients in LBDDS to streamline formulation screening and improve oral bioavailability for the three tested poorly water-soluble drugs.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationIlie, A.-R., Griffin, B. T., Vertzoni, M., Kuentz, M., Cuyckens, F., Wuyts, K., Kolakovic, R. and Holm, R. (2020) 'Toward simplified oral lipid-based drug delivery using mono-/di-glycerides as single component excipients', Drug Development and Industrial Pharmacy, (10 pp). doi: 10.1080/03639045.2020.1843475en
dc.identifier.doi10.1080/03639045.2020.1843475en
dc.identifier.endpage10en
dc.identifier.issn0363-9045
dc.identifier.journaltitleDrug Development and Industrial Pharmacyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/10811
dc.language.isoenen
dc.publisherTaylor & Francisen
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://www.tandfonline.com/doi/full/10.1080/03639045.2020.1843475
dc.rights© 2020 Informa UK Limited, trading as Taylor & Francis Group. This is an Accepted Manuscript of an article published by Taylor & Francis in Drug Development and Industrial Pharmacy on 09 Nov 2020, available online: http://www.tandfonline.com/10.1080/03639045.2020.1843475en
dc.subjectLipid-based drug delivery systemsen
dc.subjectLong versus medium chain lipid excipientsen
dc.subjectBiorelevant mediaen
dc.subjectDilution and dispersion testingen
dc.subjectIn vivo pharmacokineticsen
dc.titleToward simplified oral lipid-based drug delivery using mono-/di-glycerides as single component excipientsen
dc.typeArticle (peer-reviewed)en
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