Drug delivery : creating opportunities from pharmacokinetic challenges / Josias Hendrik Hamman

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