Enhanced gastrointestinal absorption of lipophilic drugs

The oral r oute is the preferred mode of drug administration, mainly due to comfort and patient c ompliance. As a c ons e quence of m odern drug discovery techniques (i.e., advances in in-vitro screening m ethods, the introduction of com bina t orial che mistry), the number of poor water-soluble drug c ompounds is constantly increasing, and to date, m ore than 40% of new c hemical e ntities are lipophilic and exhibit poor water s olubility [1]. These m olecules suffer f rom low oral bioavailability, and despite their pharmacological activity, f ail to proc eed to the advanced stages of research and development. A great chal lenge f acing t he pharmaceutical c ommunity is to turn these m olecules i nto orally administered medications with suf ficient bioavailability. This chapter specifies the barriers t hat lipophilic dr ugs have to traverse along the intestinal absorption process, as well as the means that can be utilized to overcome these barriers and enhance the bioavailability of the lipophilic drug. For a comprehensive view, the barriers and the corresponding possible solutions are presented according to their physiological order, i.e., preenterocyte, enterocyte, and postenterocyte barriers (Figure 6.1).