Title: Gastrointestinal Behavior of Weakly Acidic BCS Class II Drugs in Man - Case Study Diclofenac Potassium
Authors: Van Den Abeele, Jens ×
Brouwers, Joachim
Mattheus, Ruben
Tack, Jan
Augustijns, Patrick #
Issue Date: Feb-2016
Publisher: American Chemical Society and American Pharmaceutical Association
Series Title: Journal of Pharmaceutical Sciences vol:105 issue:2 pages:687-696
Article number: 10.1002/jps.24647
Abstract: This study aimed to investigate the gastrointestinal supersaturation and precipitation behavior of a weakly acidic Biopharmaceutics Classification System (BCS) Class II drug in healthy volunteers. For this purpose, a tablet containing 50 mg diclofenac potassium (Cataflam®) was predissolved in 240 mL of water and this solution was subsequently orally administered to five healthy volunteers under fasted and fed state conditions with or without concomitant use of a proton-pump inhibitor (PPI) (40 mg esomeprazole, Nexiam®). Subsequently, total diclofenac content and dissolved intraluminal drug concentrations as well as drug thermodynamic solubility were determined in gastrointestinal aspirates. In all volunteers, gastric supersaturation resulted in precipitation of diclofenac in the stomach. The extent of precipitation correlated well with gastric pH (r = - 0.78). pH dependency of precipitation was corroborated by the absence of precipitate in the stomach after coadministration of a meal and/or a PPI. Diclofenac was found to be fully dissolved in the duodenum in all test conditions. It can be concluded that substantial pH-dependent gastric precipitation of a weakly acidic BCS Class II drug administered as a solution occurs in humans. With regard to its implications for intestinal absorption, results suggest the instantaneous redissolution of gastric drug precipitate upon transfer to the duodenum. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
ISSN: 0022-3549
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Drug Delivery and Disposition
Translational Research in GastroIntestinal Disorders
× corresponding author
# (joint) last author

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