A biological modeling system and method for enhanced computer-aided analysis
of
biological response data provides information synthesized from immediate and extended
release in vivo data and in vitro data. An executable model of a biological system
is developed from information and structures based on the data. In a preferred
embodiment, a two stage approach to modeling is used in the development of an IVIVC.
The first stage of the procedure is deconvolution, where the percentage of drug
absorbed is determined. In the second stage, the in vivo percentage absorbed data
is correlated to the in vitro fraction or percentage dissolved data. This correlation
then represents a point-to-point relationship between the in vitro dissolution
and the in vivo input rate of the drug from the dosage form. In such a correlation,
the in vitro dissolution and in vivo absorption profiles are either directly superimposable
or may be made to be superimposable by the use of a scaling factor. Prior to the
deconvolution stage, a unit impulse response function can be determined from immediate-release
concentration-time data. This impulse response function is used in the deconvolution
process to determine the in vivo percent absorbed for the extended release formulations.
A nonlinear IVIVC model is developed that can incorporate time-scaling and time-shifting
into the model if needed. After the two-stage modeling is completed, the predictability
of the developed IVIVC model is evaluated by both internal and external validation.