Abstract
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 language | English |
|---|---|
| Pages (from-to) | 495-504 |
| Number of pages | 10 |
| Journal | Journal of Pharmacy and Pharmacology |
| Volume | 55 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2003 |
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ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
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Direct, differential-equation-based in-vitro-in-vivo correlation (IVIVC) method. / Buchwald, Peter.
In: Journal of Pharmacy and Pharmacology, Vol. 55, No. 4, 01.04.2003, p. 495-504.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Direct, differential-equation-based in-vitro-in-vivo correlation (IVIVC) method
AU - Buchwald, Peter
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
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U2 - 10.1211/002235702847
DO - 10.1211/002235702847
M3 - Article
C2 - 12803771
AN - SCOPUS:0038061542
VL - 55
SP - 495
EP - 504
JO - Journal of Pharmacy and Pharmacology
JF - Journal of Pharmacy and Pharmacology
SN - 0022-3573
IS - 4
ER -