Hydrophilic matrices: application of Placket-Burman screening design to model the effect of POLYOX-carbopol blends on drug release.

The aim of the present study was to screen the effect of seven factors--POLYOX molecular weight (X(1)) and amount (X(2)); carbopol (X(3)), lactose (X(4)), sodium chloride (X(5)), citric acid (X(6)); compression pressure (X(7))--on (1) the release of theophylline from hydrophilic matrices, demonstrated by changes in dissolution rate, and (2) their impact on the release exponent [n] indicative of the drug transport mechanism through the diffusion matrix. This objective was accomplished utilizing the Placket-Burman screening design. Theophylline tablets were prepared according to a 7-factor-12-run statistical model and subjected to a 24-h dissolution study in phosphate buffer at pH 7.2. The primary response variable, Y(4), was the cumulative percent of theophylline dissolved in 12h. The regression equation for the response was Y(4)=66.2167 - 17.5833X(1) - 3.3833X(2) - 9.366X(3) - 1.1166X(4) - 0.6166X(5) + 2.6X(6) - 2.783X(7). This polynomial model was validated by the ANOVA and residual analysis. The results showed that only two factors (X(2) and X(3)) had significant effect (p-value<0.10) on theophylline release from the hydrophilic polymer matrix. Factors (X(2) and X(7)) had significant effect (p-value<0.10) on [n], the exponent.