COMPUTER OPTIMIZATION FOR THE FORMULATION OF CONTROLLED-RELEASE THEOPHYLLINE TABLET MADE OF MICRONIZED LOW-SUBSTITUTED HYDROXYPROPYLCELLULOSE AND METHYLCELLULOSE

A computer optimization technique based on response surface methodolog y was applied to the formulation optimization of a controlled-release tablet made of micronized low-substituted hydroxypropylcellulose (L-HP C) and methylcellulose (MC) as matrix carriers. Theophylline was selec ted as the model drug, and was directly compressed with these carriers . Since the tablet showed slow disintegration from the outer layer, re lease was estimated to involve a coupling of diffusion and erosion rel ease mechanisms. The percentage of drug released at time i (D-i) and p ercent disintegration of the matrix not including the drug at 5h (Dis( 5)) were examined. D-i and Dis(5) decreased with an increase in the am ount of micronized L-HPC (X(1)) and with a decrease in the amount of M C (X(2)) in the tablet. In contrast, they were little affected by comp ression pressure (X(3)). These response variables-D-i and Dis(5)-were predicted well by a multiple regression equation involving the combina tion of X(1), X(2) and X(3). In the optimization study, formulation of the controlled-release tablet was examined to obtain zero-order relea se over 10 h. The predicted release rate obtained from the optimum for mula agreed well with experimental values. The result suggests that th e technique is useful for the formulation optimization of this matrix system, and that this system has the potential to control the release rate, including zero-order release profile.