ABSTRACT
Since the introduction of Caco-2 cells as an intestinal permeability model in 1989, this model has been widely applied to many areas of pharmaceutical research. Although the initial attraction to Caco-2 cells was due to the lack of alternative experimental models to screen the increasing numbers of drug candidates; it was the utility of the model in the estimation of absorption potential that drove its subsequent adaptation to other applications such as drug-transporter interactions, permeation enhancers, mechanisms of intestinal permeation, and formulation development. As a result of its widespread use in the academic, industrial, and regulatory environments across the world, it has become, by default, the gold standard for in vitro permeability studies. The Caco-2 cell model in pharmaceutical research has been cemented by its application in the context of the biopharmaceutics classification system (BCS) and transporter-mediated drug–drug interaction (DDI) guidelines. More recently, Caco-2 cells applied with novel systems such as the dissolution/permeation (D/P) chambers and In-vitro Dissolution Absorption Systems (IDAS), and using physiologically relevant experimental conditions, should help narrow the in vitro–in vivo gap, by yielding in vitro data of greater translatability to the in vivo situation.
