Three-layer matrix tablets and simple approach of drug release programming

A face-centered central composite experimental design was applied in programming the sustained drug release from three-layer matrix tablets. Xanthan gum (XG), sodium alginate (SA) and their 1:1 mixture were employed as the matrix former controlling the release of diltiazem HCl (DH). Mass fraction of DH in the intermediate layer (X) and percentage of XG in the matrix former of the intermediate and outer layers (X2 and X3, respectively) were the independent experimental variables (formulation factors). Cumulative percent release at 2 and 12 h (rel2h, rel12h), shape parameter of the release profiles in Weibull function (b), and exponent in the power law model of Peppas (n), were selected as dependent variables and related to the formulation factors via multiple linear regression analysis using second order polynomial equations including two-factor interaction terms. Simplified equations were derived and response surface analysis enabled the formulation factor effects and interactions to be visualized. It was found that different shapes of release profiles can be obtained corresponding to Weibull shape parameter (b) between 0.311 and 1.247. In general, increased incorporation of DH in the intermediate layer or of XG in the outer layers reduced the drug release because of restricted and delayed exposure to the dissolution medium or formation of a stronger diffusion barrier, respectively. Highly significant linear correlation (r = 0.894, p < 0.001) was found between the values of b and the exponent in the power law model of Peppas (n). Good agreement between the predicted, on the basis of the simplified equations (regression models), and the experimental values of three control formulations confirmed the validity of the suggested models in programming the release behavior by the proposed three-layer tablet system within the experimental domain.