Quantitative, mechanistic and physiologically realistic approach to the biopharmaceutical design of oral drug delivery systems

Abstract

The anatomical reserve length for the intestinal absorption of drugs is presented as the framework by which many physicochemical, physiological and dosage form factors are put into quantitative interrelationships. The concept is a basic science approach to the optimization of oral drug formulations and provides a perspective in the selection of strategies and options within established boundaries. The framework, thus far described here, provides the base upon which refinements and other considerations can be added. What is not covered here are considerations of absorption windows, which we have defined as that part of the small intestine where absorption occurs for special mechanistic reasons. The windows include the pH-absorption window, distribution of aqueous pore pathways along the intestinal tract, specialized membrane transport mechanisms, membrane distribution of enzyme systems and differences in transit times in the intestinal tract. We have omitted this interesting topic from the reserve length treatment since this has been discussed previously13. In the course of the theoretical discussions of the reserve length, various gaps in research were highlighted. We leave this to be further discussed by Professor W.I. Higuchi in this symposium book.