Physiological Parameters Relevant to Dissolution Testing - Hydrodynamic Considerations (rev. and suppl. version)

Abstract

The first two sections of the monograph present an introduction into basic hydrodynamics relevant to in vitro dissolution testing including V. G. Levichs convective diffusion theory and the authors combination model. This part is followed by hydrodynamic considerations of in vivo dissolution including hydrodynamic problems inherent to in vivo bioavailability of solid oral dosage forms. Hydrodynamics in the upper GI tract contribute to in vivo dissolution. Our ability to forecast dissolution of poorly soluble drugs in vitro depends on our knowledge of and ability to control hydrodynamics as well as other factors influencing dissolution. Provided suitable conditions (apparatus, hydrodynamics, media) are chosen for the dissolution test, it seems possible to predict dissolution limitations to the oral absorption of drugs and to reflect variations in hydrodynamic conditions in the upper GI tract. The fluid volume available for dissolution in the gut lumen, the contact time of the dissolved compound with the absorptive sites and the particle size have been identified as the main hydrodynamic determinants for the absorption of poorly soluble drugs in vivo. The influence of these factors is usually more pronounced than that of the motility pattern or the gastrointestinal flow rates per se.