Atenolol gastrointestinal therapeutic system: optimization of formulation variables using response surface methodology Academic Article uri icon


  • Osmotically controlled drug delivery systems are of interest for the maintenance of constant drug levels in essential hypertension. The objective of this study was to prepare and evaluate an optimized, osmotically controlled formulation of a model drug, atenolol. Preparation involved the fabrication of biconvex, bilayered tablets containing drug, an osmotic agent and other additives. Earlier studies on the screening of several variables have revealed that orifice size, coating level and the amount of Carbopol 934P have pronounced effects on the in-vitro release kinetics of atenolol. Therefore, for formulation optimization, a three-factor, three level Box-Behnken design was employed with independent variables of orifice size (X1), coating level (X2), and the amount of Carbopol 934P (X3). The response variable was cumulative percent of atenolol released with constraints on time for 10, 25, 50 and 75% release. Mathematical equations and response surface plots were used to relate independent variables with percent released in 24 h (Y5). The regression equation generated was Y5 = 19.38 + 2875.60X1 + 26.96X2 + 0.52X3 - 2410.0X1X2 + 49.68X1X3 + 0.11X2X3 - 130 729X12 + 2.24X2X2 - 0.01X32. The optimization model predicted >90% drug release with X1, X2 and X3 levels of 0.017, 2 and 163.3 respectively. Preparation and testing of the optimized formulation showed a good correlation between predicted and observed values.

published proceedings

  • Journal of Controlled Release

altmetric score

  • 3

author list (cited authors)

  • Sastry, S. V., Reddy, I. K., & Khan, M. A.

citation count

  • 40

complete list of authors

  • Sastry, Srikonda V||Reddy, Indra K||Khan, Mansoor A

publication date

  • March 1997