Theoretical Consideration: The most commonly used definition of IVIVC (In Vitro/In Vivo Correlation) is the one described in one of the FDA guidance documents (link). It defines IVIVC as a predictive mathematical model describing the relationship between an in vitro property of a 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.
In this regard, the most sought after relationship is of “Level A”, which is further defined as a predictive mathematical model for the relationship between the entire in vitro dissolution/release time course and the entire in vivo response time course, e.g., the time course of plasma drug concentration or amount of drug absorbed.
Practical Consideration: On the practical side, the purpose of IVIVC is to use drug dissolution results from two or more products to predict similarity or dissimilarity of expected plasma drug concentration (profiles). Before one considers relating in vitro results to in vivo, one has to establish as to how one will establish similarity or dissimilarity of in vivo response i.e. plasma drug concentration profiles. The methodology of establishing similarity or dissimilarity of plasma drug concentrations profile is known as bioequivalence testing. There are very well established guidances and standards available for establishing bioequivalence between drug profiles and products.
Ideally, therefore, one should focus on predicting or calculating plasma drug concentration profiles from drug dissolution results for an appropriate IVIVC. A common mathematical technique employed for this purpose is known as convolution, which basically convolutes (combines) dissolution results (profile) with plasma concentrations following intravenous (IV) drug administration to provide expected plasma concentrations for solid oral dosage forms. In mathematical terminology, dissolution results become an input function and plasma concentrations (e.g. from IV) become a weighting factor or function resulting in an output function representing plasma concentrations for the solid oral product.
Further details about this methodology and its use will be described in future posts.
