PBPK modeling software – from discovery through

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What is IVIVCPlus™?

IVIVCPlus is an optional add-on module that provides a convenient way to develop a correlation (IVIVC) between either in vitro release and in vivo release or in vitro release and absolute bioavailability. The formed correlation can then be used to either predict plasma concentration-time profiles for formulations with different in vitro release rates or, potentially, for biowaiver purposes.

GastroPlus was the first software program to offer “mechanistic deconvolutions”, which deconvolute, or fit, the in vivo dissolution vs. time along the gut lumen. An advantage to using the mechanistic deconvolution method is that it can be linked to a PBPK model (through the PBPKPlus Module). We are pleased to validate the mechanistic deconvolution method through a 5-year Research Collaboration Agreement with the U.S. FDA.

IVIVCPlus offers five methods for deconvolution:

  1. Mechanistic Absorption Model (GastroPlus™)
  2. Wagner-Nelson (1-compartment model)
  3. Loo-Riegelman (2-compartment model)
  4. Loo-Riegelman (3-compartment model)
  5. Numerical Deconvolution

The Mechanistic Absorption Model (GastroPlus) deconvolution method directly deconvolutes the in vivo release rate.The other four methods are traditional deconvolution methods that calculate the rate of appearance of compound into the systemic circulation. For formulation scientists, the correlation between in vitro release and in vivo release is much more intuitive and valuable.

Depending on the deconvolution method selected, a correlation can be made between in vitro release and in vivo release or in vitro release and absolute bioavailability. Currently, linear, power, and polynomial (second, or third order) functions may be selected for the functional form of the correlation.

Run Convolutions: the correlation function can be used to calculate an in vivo release-time profile or absolute bioavailability-time profile for a new formulation of the compound exhibiting a different in vitro release-time profile.A plasma concentration-time profile for the new formulation can be constructed with the calculated in vivo release-time or absolute bioavailability-time profile.

Evaluate Validation Statistics: after running a convolution, IVIVCPlus outputs the observed values, predicted values, prediction errors, and mean absolute percent prediction error for both Cmax and AUC.  These statistics can be used to evaluate the internal or external predictability of the correlation as described in the FDA’s “Guidance for Industry Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations”.