In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation

dc.check.infoAccess to this article is restricted until 12 months after publication by the request of the publisher.en
dc.contributor.authorMcCarthy, Carol A.
dc.contributor.authorFaisal, Waleed
dc.contributor.authorO'Shea, Joseph P.
dc.contributor.authorMurphy, Colm
dc.contributor.authorAhern, Robert J.
dc.contributor.authorRyan, Katie B.
dc.contributor.authorGriffin, Brendan T.
dc.contributor.authorCrean, Abina M.
dc.contributor.funderScience Foundation Irelanden
dc.description.abstractDrug release from mesoporous silica systems has been widely investigated in vitro using USP Type II (paddle) dissolution apparatus. However, it is not clear if the observed enhanced in vitro dissolution can forecast drug bioavailability in vivo. In this study, the ability of different in vitro dissolution models to predict in vivo oral bioavailability in a pig model was examined. The fenofibrate-loaded mesoporous silica formulation was compared directly to a commercial reference product, Lipantil Supra®. Three in vitro dissolution methods were considered; USP Type II (paddle) apparatus, USP Type IV (flow-through cell) apparatus and a USP IV Transfer model (incorporating a SGF to FaSSIF-V2 media transfer). In silico modelling, using a physiologically based pharmacokinetic modelling and simulation software package (Gastroplus™), to generate in vitro/in vivo relationships was also investigated. The study demonstrates that the in vitro dissolution performance of a mesoporous silica formulation varies depending on the dissolution apparatus utilised and experimental design. The findings show that the USP IV transfer model was the best predictor of in vivo bioavailability. The USP Type II (paddle) apparatus was not effective at forecasting in vivo behaviour. This observation is likely due to hydrodynamic differences between the two apparatus and the ability of the transfer model to better simulate gastrointestinal transit. The transfer model is advantageous in forecasting in vivo behaviour for formulations which promote drug supersaturation and as a result are prone to precipitation to a more energetically favourable, less soluble form. The USP IV transfer model could prove useful in future mesoporous silica formulation development. In silico modelling has the potential to assist in this process. However, further investigation is required to overcome the limitations of the model for solubility enhancing formulations.en
dc.description.sponsorshipScience Foundation Ireland (SFI under grant number 12/RC/2275); Synthesis and Solid State Pharmaceutical Centre (SSPC)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.identifier.citationMcCarthy, C. A., Faisal, W., O'Shea, J. P., Murphy, C., Aherne, R. J., Ryan, K. B., Griffin, B. T. and Crean, A. M. 'In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation', Journal of Controlled Release. Article in Press. doi:10.1016/j.jconrel.2016.12.043en
dc.identifier.journaltitleJournal Of Controlled Releaseen
dc.rights© 2017, Elsevier Inc. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.en
dc.subjectMesoporous silicaen
dc.subjectTransfer modelen
dc.subjectIn vitro in vivo relationship (IVIVR)en
dc.titleIn vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulationen
dc.typeArticle (peer-reviewed)en
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