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dc.contributor.authorLynnerup, Jakob Tobias
dc.contributor.authorEriksen, Jonas Borregaard
dc.contributor.authorBauer-Brandl, Annette
dc.contributor.authorHolsæter, Ann Mari
dc.contributor.authorBrandl, Martin
dc.date.accessioned2023-03-14T09:47:13Z
dc.date.available2023-03-14T09:47:13Z
dc.date.issued2023-03-02
dc.description.abstractAs numerous new drug candidates are poorly water soluble, enabling formulations are needed to increase their bioavailability for oral administration. Nanoparticles are a conceptually simple, yet resource consuming strategy for increasing drug dissolution rate, as predicting in vivo oral absorption using in vitro dissolution remains difficult. The objective of this study was to obtain insight into nanoparticle characteristics and performance utilizing an in vitro combined dissolution/permeation setup. Two examples of poorly soluble drugs were examined (cinnarizine and fenofibrate). Nanosuspensions were produced by top-down wet bead milling using dual asymmetric centrifugation, obtaining particle diameters of approx. 300 nm. DSC and XRPD studies indicated that nanocrystals of both drugs were present with retained crystallinity, however with some disturbances. Equilibrium solubility studies showed no significant increase in drug solubility over the nanoparticles, as compared to the raw APIs. Combined dissolution/permeation experiments revealed significantly increased dissolution rates for both compounds compared to the raw APIs. However, there were substantial differences between the dissolution curves of the nanoparticles as fenofibrate exhibited supersaturation followed by precipitation, whereas cinnarizine did not exhibit any supersaturation, but instead a shift towards faster dissolution rate. Permeation rates were found significantly increased for both nanosuspensions when compared to the raw APIs, indicating a direct implication that formulation strategies are needed, be it stabilization of supersaturation by precipitation inhibition and/or dissolution rate enhancement. This study indicates that in vitro dissolution/ permeation studies can be employed to better understand the oral absorption enhancement of nanocrystal formulations.en_US
dc.identifier.citationLynnerup, Eriksen, Bauer-Brandl, Holsæter, Brandl. Insight into the mechanism behind oral bioavailability-enhancement by nanosuspensions through combined dissolution/permeation studies. European Journal of Pharmaceutical Sciences. 2023en_US
dc.identifier.cristinIDFRIDAID 2133373
dc.identifier.doi10.1016/j.ejps.2023.106417
dc.identifier.issn0928-0987
dc.identifier.issn1879-0720
dc.identifier.urihttps://hdl.handle.net/10037/28738
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.journalEuropean Journal of Pharmaceutical Sciences
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleInsight into the mechanism behind oral bioavailability-enhancement by nanosuspensions through combined dissolution/permeation studiesen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Except where otherwise noted, this item's license is described as Attribution 4.0 International (CC BY 4.0)