Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine—A Study with Felodipine as a Model Drug. Issue 9 (15th May 2015)

• Record Type: Journal Article
• Authors: Lindfors, Lennart; Jonsson, Malin; Weibull, Emelie; Brasseur, James G.; Abrahamsson, Bertil; Donovan, Maureen D.; Langguth, Peter; Polli, James E.; Tamai, Ikumi; Vig, Balvinder; Yu, Lawrence X.
• Is Part Of: Journal of pharmaceutical sciences. Volume 104:Issue 9(2015:Sep.)
• Page Start: 2969
• Page End: 2976
• Publication Date: 2015-05-15
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.24487
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The aim of this study was to understand and predict the influence of hydrodynamic effects in the small intestine on dissolution of primary and aggregated drug particles. Dissolution tests of suspensions with a low‐solubility drug, felodipine, were performed in a Couette cell under hydrodynamic test conditions corresponding to the fed small intestine. Dissolution was also performed in the USP II apparatus at two paddle speeds of 25 and 200 rpm and at different surfactant concentrations below critical micelle concentration. The experimental dissolution rates were compared with theoretical calculations. The different levels of shear stress in the <italic>in vitro</italic> tests did not influence the dissolution of primary or aggregated particles and experimental dissolution rates corresponded very well to calculations. The dissolution rate for the aggregated drug particles increased after addition of surfactant because of deaggregation, but there were still no effect of hydrodynamics. In conclusion, hydrodynamics do not influence dissolution and deaggregation of micronized drug particles in the small intestine of this model drug. Surface tension has a strong effect on the deaggregation and subsequent dissolution. Addition of surfactants at <italic>in vivo</italic> relevant surface tension levels is thus critical for <italic>in vivo</italic> predictive <italic>in vitro</italic> dissolution testing. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:2969–2976, 2015</p> </abstract>