Optimization of pH-independent chronotherapeutic release of verapamil HCl from three-layer matrix tablets.

The aim of this work was to evaluate and optimize formulation of three-layer matrix tablets based on xanthan gum (XG) and sodium alginate for chronotherapeutic pH-independent release of verapamil HCl (VH). Artificial neural networks (ANN) were applied in the optimization and compared with multiple linear regression (MLR). A face-centered central composite experimental design was employed with three factors (mass fraction of VH in intermediate layer, X1, and of XG in matrix former of intermediate and outer layers, X2 and X3).