The influence of hydrodynamics on the dissolution of poorly soluble drugs

Dissolution testing is an important tool in forecasting the in vivo performance of drugs and their formulations. In recent years many efforts have been made to modify the in vitro conditions so that they better simulate in vivo behaviour. However, Iittle is known about in vivo hydrodynamics and how weil the in vitro testing conditions correspond to them. Aprerequisite to modelling in vivo hydrodynamics with a dissolution test system is to characterize the in vivo hydrodynamics in such a way that the results can be adapted to the in vitro setting. A fistulated dog model was therefore established to selectively study the influence of the particle size and GI hydrodynamic conditions on the in vivo dissolution. On the basis of its poor solubility (aqueous solubility: 1 mg/I at 37°C), high lipophilicity (log P 4.5), suitable pharmacokinetics and the availability of a variety of particle sizes, the neutral and stable antihypertensive drug felodipine was chosen as a model substance for investigating hydrodynamic effects on dissolution in both the canine model and in vitro.