Aqueous-Based Polymeric Dispersion: Face-Centered Cubic Design for the Development of Atenolol Gastrointestinal Therapeutic System

Abstract

The main objective of the study was to use the statistical response surface methodology to evaluate the effect of formulation variables and their interaction on drug release in atenolol gastrointestinal therapeutic system (GITS) development coated with cellulose acetate (CA) pseudolatex system. A three-factor, three-level, face-centered design was employed to evaluate the quadratic response surface, and to achieve the desired response in atenolol delivery. Coating was achieved by spraying plasticized CA pseudolatex on atenolol bilayered tablets in a Uni-Glatt fluidized-bed coater. The independent variables were orifice size (X1), percent coating weight gain (X2) and Carbopol 934P (X3). The response variable (Y1) was time for 50% (t50%) drug dissolution with a constraint on cumulative percent released in 24 hr (Y2). The polynomial equation obtained was Y1 = 61.88 - 3779.8X1 + 1.89X2 - 3.95X3 - 266.87 X1X2 - 1675X1X3 + 0.07X2X3 + 215123X1(2) + 0.06X2(2) + 0.10X3(2). Contour and response plots were used to relate the independent and dependent variables. The optimization procedure predicted a t50% of 10.83 hr with 92% atenolol release in 24 hr when orifice size (X1), percent coating weight gain (X2), and Carbopol 934P (X3) were 0.014 in., 13%, and 20 mg, respectively. Preparation and testing of optimized formulation showed a good correlation between the predicted and observed values.