An IVIVC (in vitro-in vivo correlation) is a predictive mathematical model describing the relationship between the in vitro properties of a dosage form and the in vivo responses. Drug developers frequently find IVIVCs useful for a number of reasons:

They can use dissolution tests as a surrogate for human bioequivalence (BE) studies.
They can support and/or validate the use of dissolution methods and specifications.
They can assist in quality control during manufacturing and selecting appropriate formulations.
Conventional IVIVC uses deconvolution methods such as Wagner Nelson (WN) and numerical deconvolution to estimate the rate of input of drug into the systemic circulation from observed plasma drug concentrations of the oral formulation with the use of IV bolus data as the unit impulse response (UIR). To help our customers generate these models, we offer the IVIVC Toolkit for Phoenix WinNonlin.

Clearly, there have been many instances of successful use of conventional IVIVC models, and numerical deconvolution remains the gold standard. However, there are also cases where conventional models have performed very badly. One reason for this may be that conventional methods do not separately consider the multiple mechanisms that determine a drug’s in vivo input rate— transit time, gut wall permeability, gut wall metabolism, and hepatic first-pass metabolism— from dissolution rate. In this blog post, I’ll discuss our work to develop physiologically-based pharmacokinetic (PBPK), mechanistic IVIVC and why you should consider using this approach when designing and evaluating the performance and safety of new drug formulations.