ABSTRACT
Absorption of a compound from the gastrointestinal tract (GIT)
requires the availability of the compound in a solution or solubilized
form and its diffusion into and across the enterocytes lining
the intestinal lumen (Fig. 18.1).1,2 The advent of combinatorial
chemistry and high-throughput screening (HTS) resulted in the
identification of many highly potent compounds that usually have
less than desirable biopharmaceutical properties, e.g., low aque-
ous solubility and high lipophilicity.3,4 These compounds exhibit
extremely low aqueous solubility throughout the physiological
pH range, resulting in low and inconsistent oral bioavailability.5,6
Poor aqueous solubility has been identified as the single largest
physicochemical challenge for the oral absorption of compounds
Figure 18.1 Schematic of factors influencing bioavailability of an orally administered compound.
