Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine—A Study with Felodipine as a Model Drug Lennart Lindfors, Malin Jonsson,

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Hydrodynamic Effects on Drug Dissolution and Deaggregation in the Small Intestine—A Study with Felodipine as a Model Drug Lennart Lindfors, Malin Jonsson, Emelie Weibull, James G. Brasseur, Bertil Abrahamsson Journal of Pharmaceutical Sciences Volume 104, Issue 9, Pages 2969-2976 (September 2015) DOI: 10.1002/jps.24487 Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association Terms and Conditions

Figure 1 Comparisons of experimentally determined (dots) diffusion layer thickness around dissolving particles of oxazepam (blue) and digoxin (green) (Bisrat 1992) and theoretical predictions (solid lines) based on Fick’s first law. Journal of Pharmaceutical Sciences 2015 104, 2969-2976DOI: (10.1002/jps.24487) Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association Terms and Conditions

Figure 2 Design of the Couette cell. Journal of Pharmaceutical Sciences 2015 104, 2969-2976DOI: (10.1002/jps.24487) Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association Terms and Conditions

Figure 3 Particle size distributions determined by laser diffraction for felodopine (a) primary particle suspension (red) and (b) aggregated suspension (green). Journal of Pharmaceutical Sciences 2015 104, 2969-2976DOI: (10.1002/jps.24487) Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association Terms and Conditions

Figure 4 The mean (n=2) felodipine dissolution time profile in the Couette cell using density-matched medium for primary (red dots) and aggregated (green dots) particle suspension at low (5rpm) (light color dots) and intense (100rpm) (dark color dots) stirring together with theoretical dissolution prediction based on Fick’s first law for primary particle suspension (solid line). Journal of Pharmaceutical Sciences 2015 104, 2969-2976DOI: (10.1002/jps.24487) Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association Terms and Conditions

Figure 5 Mean and range (n=2) dissolution profiles for felodipine from primary (red dots) and aggregate (green dots) particle suspensions in USP II paddle apparatus in water at 25 (light color dots) and 200rpm (dark color dots) paddle stirring speed together with theoretical predictions based on Fick’s first law for primary (dark red solid line) and aggregated (dark green solid line) particles. Journal of Pharmaceutical Sciences 2015 104, 2969-2976DOI: (10.1002/jps.24487) Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association Terms and Conditions

Figure 6 Mean and range (n=2) dissolution profiles for felodipine aggregate particle suspensions in USP II paddle apparatus in water with different concentrations of SDS at 25 and 200rpm paddle stirring speed (0.1mM SDS/25rpm blue dot, 0.1mM SDS/200rpm black triangle, 1mM/25rpm red square, 1mM/200rpm dark red diamond) together with theoretical predictions based on Fick’s first law for primary (red solid line) and aggregated (green solid line) particles. Journal of Pharmaceutical Sciences 2015 104, 2969-2976DOI: (10.1002/jps.24487) Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association Terms and Conditions