Direct, differential-equation-based in-vitro-in-vivo correlation (IVIVC) method

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48 Scopus citations


A new, differential equation-based in-vitro-in-vivo correlation (IVIVC) method is proposed that directly relates the time-profiles of in-vitro dissolution rates and in-vivo plasma concentrations by using one- or multi-compartment pharmacokinetic models and a corresponding system of differential equations. The rate of in-vivo input is connected to the rate of in-vitro dissolution through a general functional dependency that allows for time scaling and time shifting. A multiplying factor that accounts for the variability of absorption conditions as the drug moves along is also incorporated. Two data sets incorporating slow-, medium-, and fast-release formulations were used to test the applicability of the method, and predictive powers were assessed with a leave-one-formulation-out approach. All fitted parameters had realistic values, and good or acceptable fits and predictions were obtained as measured by plasma concentration mean squared errors and percent AUC errors. Introduction of step-down functions that account for the transit of the dosage form past the intestinal sites of absorption proved useful. By avoiding the integral transforms used in the existing deconvolution- or convolution-based IVIVC models, the present method can provide increased transparency, improved performance, and greater modelling flexibility.

Original languageEnglish (US)
Pages (from-to)495-504
Number of pages10
JournalJournal of Pharmacy and Pharmacology
Issue number4
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science


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