Kinetics of Drugs in the Preabsorptive Phase During Their Transit-Time in the Gastrointestinal Tract

Abstract

During the transit of orally administered drugs in the GI tract, they are exposed to variable hJtile environments. The drug is subject to a wide pH range from an acidic stlmach to an alkaline small intestine and colon, as well as a variety of digttive enzymes in the gastric and intestinal fluids, and metabolizing enzyles within the intestinal wall. This, in addition to endogenous substances that affect the physical characteristics of the . environment such as bile salts and bile acids. Such conditions.are expected

to affect drug solubility( dissolution rate and permeation through the

intestinal wall, ultimately affecting its biological activity. .

Another factor to be cJsidered is gastric emptying which is governed by GI motility, and could lpact the rate of drug arrival to its absorption site. The oral route of drug aldministration is the easiest and most convenient way of non-invasive doling. The purpose of this research was to

investigate the effect of some GI parameters on the dissolution rate,

solubility, intestinal permeability and pharmacokinetic parameters of

selected model drugs.

The experimental part of this thesis was carried out at the College of

Pharmacy, University of Michigan, USA.