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. (c) 2005 Elsevier B.V. All rights reserved.