Experiments in-vitro and in dogs were conducted to find in-vitro hydrodynamic conditions that can be used to represent gastrointestinal motility patterns. Specifically, the dissolution performance of micronised and coarse-grade felodipine (a poorly soluble, neutral, lipophilic drug) was studied in a biorelevant medium in the USP paddle apparatus at various paddle speeds. Ratios of percentage dissolved (slower:faster rev min(-1)) were calculated pairwise. These ratios were then compared with AUC ratios obtained in a corresponding pharmacokinetic study in Labradors, in which the absorption of both the micronised and coarse-grade felodipine had been compared under two gastrointestinal hydrodynamic conditions. Using a paddle speed combination of 75 and 125 rev min(-1) to represent the motility patterns in response to administration of normal saline and 5% glucose, respectively, the in-vitro ratios (75:125 rev min(-1) dissolution ratio was 91% for the micronised and 46% for the coarse-grade powder) showed good agreement with the pharmacokinetic data (saline-to-glucose absorption ratio was 98% for the micronised and 46% for the coarse-grade powder). It was concluded that, provided an appropriate composition is chosen for the dissolution test, the USP paddle apparatus can be used to reflect variations in hydrodynamic conditions in the upper gastrointestinal tract.
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.
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