Drug delivery : creating opportunities from pharmacokinetic challenges / Josias Hendrik Hamman
Abstract
A drug faces several challenges after oral administration
before the site of action is reached. The major obstacles to
drug delivery after oral administration include enzymatic
degradation, the physical barrier of the intestinal epithelial
membrane, active efflux back into the lumen of the
gastrointestinal tract and biliary excretion. As more and more
drugs are developed that exhibit poor membrane permeability,
the issue of drug absorption enhancement becomes
increasingly important in drug research. Strategies to improve
the oral bioavailability of drugs can be divided into two groups
namely chemical modifications and formulation technologies.
Chemical modifications include pro-drug design and or
changing the structure of the drug in such a way to improve
solubility or membrane permeability. Formulation
technologies include the use of absorption enhancing agents,
efflux inhibitors, enzyme inhibitors, mucoadhesive systems
and particulate carrier systems. Absorption enhancing agents
increase drug membrane permeability through different
mechanisms such as tight junction regulation and efflux
inhibition. Although many chemical compounds have been
investigated for their drug absorption enhancing properties,
some caused toxicity and damaging effects to the intestinal
epithelium. However, some absorption enhancing agents
have been identified that cause a reversible effect on the
intestinal epithelium and thereby show potential to be included
in clinically effective drug delivery systems.