In vitro–in vivo correlation: Perspectives on model development

In vitro–in vivo correlation (IVIVC) allows prediction of the in vivo performance of a drug based on the in vitro drug release profiles. To develop an effective IVIVC, the physicochemical and biopharmaceutical properties of the drug as well as the physiological environment in the body must be taken into consideration. Key factors include drug solubility, pKa, drug permeability, octanol–water partition coefficient and pH of environment. In general, construction of an IVIVC involves three stages of mathematical manipulation: construct a functional relationship between input (in vitro dissolution) and output (in vivo dissolution); establish a structural relationship using data collected; parameterize the unknowns in the structural model. Some key mathematical relationships used in IVIVC development are presented. The establishment of an effective IVIVC has important implications in quality control and regulatory compliance.