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Title: Evaluation of fasted and fed state simulated and human intestinal fluids as solvent system in the Ussing chambers model to explore food effects on intestinal permeability
Authors: Wuyts, Ben ×
Riethorst, Danny
Brouwers, Joachim
Tack, Jan
Annaert, Pieter
Augustijns, Patrick #
Issue Date: 30-Jan-2015
Publisher: Elsevier/North Holland
Series Title: International Journal of Pharmaceutics vol:478 issue:2 pages:736-744
Abstract: The Ussing chambers model is almost exclusively used in the presence of plain aqueous phosphate buffers as solvent system. In an attempt to further elucidate the effect of luminal ingredients and postprandial conditions on intestinal permeability, pooled fasted and fed state human intestinal fluids (FaHIFpool, FeHIFpool) were used. In addition, simulated intestinal fluids of both nutritional states (FaSSIF, FeSSIF) were evaluated as possible surrogate media for HIF. The use of FaHIFpool generated a broad range of Papp values for a series of 16 model drugs, ranging from 0.03×10(-6)cm/s (carvedilol) to 33.8×10(-6)cm/s (naproxen). A linear correlation was observed between Papp values using FaSSIF and FaHIFpool as solvent system (R=0.990), justifying the use of FaSSIF as surrogate medium for FaHIF in the Ussing chambers. In exclusion of the outlier carvedilol, a strong sigmoidal relationship was found between Papp and fahuman of 15 model drugs, illustrated by correlation coefficients of 0.961 and 0.936 for FaHIFpool and FaSSIF, respectively. When addressing food effects on intestinal permeability, the use of FeHIFpool resulted in a significantly lower Papp value for nine out of sixteen compounds compared to fasting conditions. FeSSIF as solvent system significantly overestimated Papp values in FeHIFpool. To conclude, the optimized Ussing chambers model using biorelevant media as apical solvent system holds great potential to investigate food effects in a more integrative approach, taking into account drug solubilisation, supersaturation and formulation effects.
ISSN: 0378-5173
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
Field of Study Social and Community Work Odisee
Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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