In Vitro – In Vivo Correlation : Importance of Dissolution in IVIVC

Introduction Correlations between in vitro and in vivo data (IVIVC) are often used during pharmaceutical development in order to reduce development time and optimize the formulation. A good correlation is a tool for predicting in vivo results based on in vitro data. IVIVC allows dosage form optimization with the fewest possible trials in man,fixes dissolution acceptance criteria,and can be used as a surrogate for further bioequivalence studies; it is also recommended by regulatory authorities (1–5). Many studies reported in the late ’70s and early ’80s established the basic concept of IVIVC (6). Various definitions of in vitro–in vivo correlation have been proposed by the International Pharmaceutical Federation (FIP), the USP working group (7),and regulatory authorities such as the FDA or EMEA (2–5). The FDA (2) defines IVIVC as “a predictive mathematical model describing the relationship between an in vitro property of an extended release dosage form (usually the rate or extent of drug dissolution or release) and a relevant in vivo response,e.g.,plasma drug concentration or amount of drug absorbed.” As stressed in this definition, IVIVC is more an in vitro–in vivo relationship than a strict correlation. It should be kept in mind that a relationship does not imply a causality link between the in vitro data, in our case,and the in vivo data. Bases on the type of data used to establish the relationship, three main levels are defined by the FDA: