CHAPTER 2:Role of Solubility, Permeability and Absorption in Drug Discovery and Development

While drug absorption, one of the most important determinants of systemic drug availability, is difficult to measure in vivo, there are in vitro techniques for determining solubility and permeability, the principal components of drug absorption. Solubilization approaches have led to the development of formulations with improved in vivo absorption. Permeability is influenced by the physicochemical properties of drugs and by biological factors such as pH, enzymes, transporters, and transit time; thus, not surprisingly, it shows larger inter-laboratory variability than solubility values. This variability prevents the pooling of in vitro data from multiple laboratories to create large and reliable databases for the development of in silico models that could be used to predict in vivo absorption. Alternatively, efforts have been made to develop better in vitro models of in vivo absorption. For example, the In vitro Dissolution Absorption System (IDAS) model allows concurrent evaluation of solubility and permeability across Caco-2 monolayers, after application of drug formulations in powder form (i.e. a macerated tablet or capsule). This system is likely to help fill the void between traditional in vitro measurements and in vivo drug absorption by facilitating formulation development and the prediction of the in vivo performance of drug formulations from in vitro dissolution and permeability data.