Arik Dahan
Ben-Gurion University of the Negev, Israel
Title: Implications of Segmental-Dependent Intestinal Permeability in Oral Drug Delivery
Biography
Biography: Arik Dahan
Abstract
On several levels, the dissolution and the permeability are related and should maintain a certain relationship between them. For instance, Tsume and Amidon (Mol Pharmaceutics 2010) have shown that the higher the permeability is, the more lax the dissolution criterion for granting a bio waiver can be. In this talk, regional-dependent intestinal permeability will be discussed, including dissolution aspects, as well as pathophysiological conditions. Permeability is location dependent, and pertains to each point throughout the gastrointestinal tract. A drug may exhibit significantly different intestinal permeability not only between the small and large intestine, but even within the small intestine, i.e. between the proximal jejunum and the distal ileum. The asymmetrical pH profile throughout the small intestine may be the underling mechanism for such segmental-dependent permeability of certain ionisable drugs. An asymmetrical expression pattern of different transporters throughout the intestinal tract may also cause such regional-dependent permeability. Asymmetrical intestinal enzymes expression may significantly influence the systemic bioavailability of a drug, although not necessarily affect the permeability. In these cases, rapid vs. sustained dissolving drug products may result unexpectedly different systemic drug levels. In conclusion, it is prudent to consider the intestinal permeability pattern when deciding on a certain dissolution profile.