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

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dc.contributor.author McCarthy, Carol A.
dc.contributor.author Faisal, Waleed
dc.contributor.author O'Shea, Joseph P.
dc.contributor.author Murphy, Colm
dc.contributor.author Ahern, Robert J.
dc.contributor.author Ryan, Katie B.
dc.contributor.author Griffin, Brendan T.
dc.contributor.author Crean, Abina M.
dc.date.accessioned 2017-01-31T16:22:00Z
dc.date.available 2017-01-31T16:22:00Z
dc.date.issued 2017-01-27
dc.identifier.citation McCarthy, 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.2016.12.043 en
dc.identifier.issn 0168-3659
dc.identifier.uri http://hdl.handle.net/10468/3547
dc.identifier.doi 10.1016/j.jconrel.2016.12.043
dc.description.abstract Drug 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.sponsorship Science Foundation Ireland (SFI under grant number 12/RC/2275); Synthesis and Solid State Pharmaceutical Centre (SSPC) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
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.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Mesoporous silica en
dc.subject Dissolution en
dc.subject Transfer model en
dc.subject Hydrodynamics en
dc.subject Supersaturation en
dc.subject In vitro in vivo relationship (IVIVR) en
dc.subject Fenofibrate en
dc.title In vitro dissolution models for the prediction of in vivo performance of an oral mesoporous silica formulation en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Abina Crean, School Of Pharmacy, University College Cork, Cork, Ireland. +353-21-490-3000 Email: a.crean@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by the request of the publisher. en
dc.check.date 2018-01-27
dc.date.updated 2017-01-31T16:10:26Z
dc.description.version Accepted Version en
dc.internal.rssid 380364506
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Journal Of Controlled Release en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress a.crean@ucc.ie en
dc.internal.IRISemailaddress w.faisal@ucc.ie en


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© 2017, Elsevier Inc. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. Except where otherwise noted, this item's license is described as © 2017, Elsevier Inc. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
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