IVIVC

IVIVC, or in vitro-in vivo correlation, is a predictive mathematical relationship between a drug’s in vitro dissolution data and its in vivo absorption profile. It is used to forecast how a orally administered drug will perform in the body based on laboratory dissolution testing, aiding formulation development, quality control, and regulatory decisions.

There are three commonly described levels of IVIVC. Level A is a point-to-point correlation that links the entire in vitro dissolution curve to the in vivo plasma concentration-time profile, enabling prediction of the complete in vivo outcome from dissolution data. Level B describes a correlation of statistical moments, such as means and variances, between in vitro and in vivo measures rather than a full profile. Level C relates a single pharmacokinetic parameter, such as AUC or Cmax, to a dissolution parameter, providing a more limited predictive capability.

Developing an IVIVC involves generating robust in vitro dissolution data under biorelevant conditions and obtaining corresponding in vivo data. Techniques such as deconvolution may be used to relate observed plasma concentrations to in vivo input, after which regression analysis links the dissolved fraction to the absorbed fraction. The approach is most successful for drugs with consistent absorption and dissolution behavior and for dosage forms where the release mechanism dominates in vivo performance.

Applications of IVIVC include optimizing formulations, supporting regulatory discussions, and potentially enabling biowaivers for certain product changes without repeated in vivo studies. Limitations include variability in gastric conditions, absorption windows, solubility and permeability, and complex metabolism or transport effects. IVIVC remains a valuable tool in biopharmaceutics when developed with appropriate biorelevant dissolution methods and high-quality in vivo data.