P. Macheras et P. Argyrakis, GASTROINTESTINAL DRUG ABSORPTION - IS IT TIME TO CONSIDER HETEROGENEITY AS WELL AS HOMOGENEITY, Pharmaceutical research, 14(7), 1997, pp. 842-847
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.