In Vitro-In Vivo Correlation (IVIVC): From Current Achievements Towards the Future

Abstract

Conventional in vitro-in vivo correlation (IVIVC) based on compendial dissolution testing faces many obstacles, among which are problems in establishing meaningful correlation for immediate release dosage forms, lack of intravenous data in cases of many drugs without a possibility to obtain a unit impulse response, and well-known difficulties to build an IVIVC model for BCS III and BCS IV class drugs. Three major elements are obligatory for IVIVC development: in vitro dissolution data, in vivo pharmacokinetic profile, and modeling tools. Dissolution testing and modeling approaches are under heavy development to create predictive IVIVIC/IVIVR models. Application of noncompendial dissolution methods, biorelevant media, and equipment simulating the human gastrointestinal tract, together with sophisticated multivariate statistical methods and mechanistic approaches, are nominated to be the future of IVIVC.

Physiologically Based Pharmacokinetic (PBPK) Modelling for In Vitro-In Vivo Extrapolation: Emphasis on the Use of Dissolution Data

“…According to the US Food and Drug Administration's (FDA) guidelines, a high level of IVIVC should establish a pointto-point overlap between the in vitro dissolution and the in vivo drug concentration profiles (28). The generation of IVIVC can be carried out using either one-stage convolution or a two-stage deconvolution approach.…”