Coupling biorelevant dissolution methods with physiologically based pharmacokinetic modelling to forecast in-vivo performance of solid oral dosage forms

OBJECTIVES: To summarize the basis for and progress with the development of in-vitro-in-silico-in-vivo (IV-IS-IV) relationships for oral dosage forms using physiologically based pharmacokinetic (PBPK) modelling, with the focus on predicting the performance of solid oral dosage forms in humans. KEY FINDINGS: Various approaches to forecasting oral absorption have been reported to date. These range from simple dissolution tests, through biorelevant dissolution testing and laboratory simulations of the gastrointestinal (GI) tract, to the use of PBPK modelling to predict oral drug absorption based on the physicochemical parameters of the drug substance. Although each of these approaches can be useful for qualitative predictions, forecasting oral absorption on a quantitative basis with an individual approach is only possible for selected drug/dosage form combinations. By integrating biorelevant dissolution test results with the PBPK models, it has become possible to achieve quantitatively accurate as well as qualitative predictions of plasma profiles after oral dosing for both immediate and modified release formulations. SUMMARY: With further refinement of both the biorelevant dissolution testing methods and the PBPK models, it should be possible to expedite the development and regulatory approval of optimized dosage forms and dosing conditions.