GASTROINTESTINAL DRUG ABSORPTION - IS IT TIME TO CONSIDER HETEROGENEITY AS WELL AS HOMOGENEITY

The current analysis of gastrointestinal absorption phenomena relies o n the concept of homogeneity. However, drug dissolution, transit and u ptake in the gastrointestinal tract are heterogeneous processes since they take place at interfaces of different phases under variable stirr ing conditions. Recent advances in physics and chemistry demonstrate t hat the geometry of the environment is of major importance for the tre atment of heterogeneous processes. In this context, the heterogeneous character of in vivo drug dissolution, transit and uptake is discussed in terms of fractal concepts, Based on this analysis, drugs are class ified in accordance with their gastrointestinal absorption characteris tics into two broad categories i.e. homogeneous and heterogeneous. The former category includes drugs with satisfactory solubility and perme ability which ensure the validity of the homogeneous hypothesis. Drugs with low solubility and permeability are termed heterogeneous since t hey traverse the entire gastrointestinal tract and therefore are more likely to exhibit heterogeneous dissolution, transit and uptake. The h igh variability of whole bowel transit and the unpredictability of con ventional dissolution tests for heterogeneous drugs are interpreted on the basis of the fractal nature of these processes under in vivo cond itions. The implications associated with the use of strict statistical criteria in bioequivalence studies for heterogeneous drugs are also p ointed out.