PURPOSE: To study the influence of GI hydrodynamics and drug particle size on felodipine absorption in the dog. METHODS: Labradors fistulated at midjejunum were used to selectively study the influence of hydrodynamics and particle size on the in vivo dissolution and absorption of the poorly soluble, lipophilic drug felodipine. A combination of infusion and oral administration of either normal saline or a 5% glucose solution was used to maintain "fasted" and establish "fed" state motility patterns, respectively. The absorption characteristics of both a micronized (8 microm) and a coarse fraction (125 micom) of felodipine were subsequently studied under these two motility patterns. RESULTS: A reduction in particle size led up to an approximate 22-fold increase in maximum plasma concentration and up to an approximate 14-fold increase in area under the curve, with a commensurate decrease in the time at which the maximum plasma concentration occurred. Although the absorption of felodipine from the solution and micronized suspension was not influenced by a change in the hydrodynamics, felodipine was absorbed from the coarse suspension almost twice as well in the "fed" state as under "fasted" conditions. CONCLUSIONS: Absorption from coarse suspensions of felodipine was sensitive to luminal hydrodynamics, whereas micronized suspensions were not. However, the particle size seems to have a much more important influence on the bioavailability of felodipine than the hydrodynamics per se.
PURPOSE: To study the influence of GI hydrodynamics and drug particle size on felodipine absorption in the dog. METHODS: Labradors fistulated at midjejunum were used to selectively study the influence of hydrodynamics and particle size on the in vivo dissolution and absorption of the poorly soluble, lipophilic drug felodipine. A combination of infusion and oral administration of either normal saline or a 5% glucose solution was used to maintain "fasted" and establish "fed" state motility patterns, respectively. The absorption characteristics of both a micronized (8 microm) and a coarse fraction (125 micom) of felodipine were subsequently studied under these two motility patterns. RESULTS: A reduction in particle size led up to an approximate 22-fold increase in maximum plasma concentration and up to an approximate 14-fold increase in area under the curve, with a commensurate decrease in the time at which the maximum plasma concentration occurred. Although the absorption of felodipine from the solution and micronized suspension was not influenced by a change in the hydrodynamics, felodipine was absorbed from the coarse suspension almost twice as well in the "fed" state as under "fasted" conditions. CONCLUSIONS: Absorption from coarse suspensions of felodipine was sensitive to luminal hydrodynamics, whereas micronized suspensions were not. However, the particle size seems to have a much more important influence on the bioavailability of felodipine than the hydrodynamics per se.
Authors: Leonard G McCarthy; Carolin Kosiol; Anne Marie Healy; Geoff Bradley; James C Sexton; Owen I Corrigan Journal: AAPS PharmSciTech Date: 2003 Impact factor: 3.246
Authors: Maria Vertzoni; Amalia Diakidou; Manos Chatzilias; Erik Söderlind; Bertil Abrahamsson; Jennifer B Dressman; Christos Reppas Journal: Pharm Res Date: 2010-07-30 Impact factor: 4.200
Authors: Eva M Persson; Ann-Sofie Gustafsson; Anders S Carlsson; Ralf G Nilsson; Lars Knutson; Patrick Forsell; Gunilla Hanisch; Hans Lennernäs; Bertil Abrahamsson Journal: Pharm Res Date: 2005-10-30 Impact factor: 4.200