Optimization of a matrix tablet formulation using a mixture design.

The simplex centroid design was applied to the optimization of a modified release tablet formulation. A base granulation was made with the active ingredient naftidrofuryl. The variables investigated included fractions of the excipients microcrystalline cellulose, lactose and dicalcium phosphate dihydrate. The release rate, crushing strength, friability and weight variation were determined as response parameters. Mathematical models were fitted to the data obtained by the lattice method, described by Scheffé and by means of multiple linear regression. Regression analysis indicated a relatively good fit of the models. On the basis of the regression models, contour plots were constructed. An increase in the amount of dicalcium phosphate caused lower release rate and increased weight variation. An increase in the content of lactose showed lower strength and increased friability, whereas an increase in the amount of microcrystalline cellulose had the opposite effect.