The Optimization Module for GastroPlus™ is an optional add-on module that extends and enhances the program's basic capabilities in several very powerful ways. The Optimization Module provides a researcher with the ability to easily "optimize" input parameters to fit simulation results to experimental data. With the functionality that the Optimization Module provides, researchers can:

• Automatically fit model parameters to data
• Deconvolute in vivo release versus time from oral plasma concentration-time data
• Design formulations to achieve target plasma concentration-time profiles



The Optimization Module utilizes a multivariate nonlinear optimization scheme to optimize a set of variables selected by the user from a list of possible input parameters.

Model parameters can be fitted to data for a single record, or across multiple records simultaneously.

Model Building
"Building models" means optimizing certain input parameters to calibrate the simulation to a particular congeneric series of drugs, or to better predict a single drug.

To build a model, you may assemble a database of compounds with known permeabilities, fractions dose absorbed, and, if available, pharmacokinetic parameters and plasma concentration-time data. You can then program the Optimization Module to adjust the absorption scale factors in as many compartments as desired. The Optimization Module will run a series of simulations, continuously adjusting the selected parameters in order to minimize the differences between predicted results and observed data. Absorption scale factors that are not selected are constrained to be equal to the absorption scale factor for the preceding compartment.

Deconvolution
The ability of the Optimization Module to adjust any of the absorption, pharmacokinetic, or controlled release parameters to fit predicted results to observed data for a single drug means that the Optimization Module can be used for the deconvolution of experimental data. With this capability, you can use the basic simulation model provided by Simulations Plus, or your own model developed as described above, and can allow the Optimization Module to adjust unknown (or low confidence) parameters to match oral plasma concentration-time data.

Formulation and Controlled Release Profile Design
Once an accurate model has been derived for a particular compound, the Optimization Module can be used to adjust formulation variables (solubility, particle density, dose, and radius) or percent released versus time for controlled release drugs, to achieve a target plasma concentration-time profile. This capability of the Optimization Module provides you with a way to specify formulation parameters needed to achieve therapeutic goals.

For further information about licensing the Optimization Module, please contact:

Mr. John DiBella
Director, Marketing & Sales
661-723-7723 ext. 244
john.dibella@simulations-plus.com