ATENOLOL GASTROINTESTINAL THERAPEUTIC SYSTEM - OPTIMIZATION OF FORMULATION VARIABLES USING RESPONSE-SURFACE METHODOLOGY

Osmotically controlled drug delivery systems are of interest for the m aintenance of constant drug levels in essential hypertension. The obje ctive of this study was to prepare and evaluate an optimized, osmotica lly controlled formulation of a model drug, atenolol. Preparation invo lved the fabrication of biconvex. bilayered tablets containing drug, a n osmotic agent and other additives. Earlier studies on the screening of several variables have revealed that orifice size, coating level an d the amount of Carbopol(R) 934P have pronounced effects on the in-vit ro release kinetics of atenolol. Therefore, for formulation optimizati on, a three-factor, three level Box-Behnken design was employed with i ndependent variables of orifice size (X(1)), coating level (X(2)), and the amount of Carbopol(R) 934P (X(3)). The response variable was cumu lative percent of atenolol released with constraints on time for 10, 2 5, 50 and 75% release. Mathematical equations and response surface plo ts were used to relate independent variables with percent released in 24 h (Y-5). The regression equation generated was .11X(2)X(3)-130729X( 1)(2)+2.24X(2)(2)-0.01X(3)(2). The optimization model predicted >90% d rug release with X(1), X(2) and X(3) levels of 0.017, 2 and 163.3 resp ectively. Preparation and testing of the optimized formulation showed a good correlation between predicted and observed values.