Lipidic dispersion to reduce food dependent oral bioavailability of fenofibrate: In vitro, in vivo and in silico assessments.

Autor: O'Shea JP; Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland., Faisal W; Faculty of Pharmacy, Minia University, Egypt., Ruane-O'Hora T; Department of Physiology, University College Cork, Ireland., Devine KJ; Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland., Kostewicz ES; Institut für Pharmazeutische Technologie, Goethe Universität, Frankfurt am Main, Germany., O'Driscoll CM; Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland., Griffin BT; Pharmacodelivery Group, School of Pharmacy, University College Cork, Ireland. Electronic address: brendan.griffin@ucc.ie.
Jazyk: angličtina
Zdroj: European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V [Eur J Pharm Biopharm] 2015 Oct; Vol. 96, pp. 207-16. Date of Electronic Publication: 2015 Jul 26.
DOI: 10.1016/j.ejpb.2015.07.014
Abstrakt: Novel formulations that overcome the solubility limitations of poorly water soluble drugs (PWSD) are becoming ever more critical to a drug development process inundated with these compounds. There is a clear need for developing bio-enabling formulation approaches to improve oral bioavailability for PWSD, but also to establish a range of predictive in vitro and in silico biopharmaceutics based tools for guiding formulation design and forecasting in vivo effects. The dual aim of this study was to examine the potential for a novel lipid based formulation, termed a lipidic dispersion, to enhance fasted state oral bioavailability of fenofibrate, while also assessing the predictive ability of biorelevant in vitro and in silico testing. Formulation as a lipidic dispersion improved both dissolution and solubilisation of fenofibrate through a combination of altered solid state characteristics and incorporation of solubilising lipidic excipients. These changes resulted in an increased rate of absorption and increased maximal plasma concentrations compared to a commercial, micronised product (Lipantil® Micro) in a pig model. Combination of biorelevant in vitro measurements with in silico physiologically based pharmacokinetic (PBPK) modelling resulted in an accurate prediction of formulation performance and forecasts a reduction in food effects on fenofibrate bioavailability through maximising its fasted state dissolution.
(Copyright © 2015 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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