Optimization of the gastroretentive system for controlled oral administration of cinnarizine using response surface methodology

Abstract

the gastroretentive administration of decynarizine. To produce controlled release floating cinnarizine tablets by direct compression, a Box-Behnken 33 design was used. The effects of formulation variables such as the levels of HPMC K4M (X1), sodium bicarbonate (X2) and citric acid (X3) were studied. on tablet buoyancy characteristics and drug release. Response parameters such as total buoyancy time (TFT), release after 10 h (Rel10), time required for 50% release of the drug (t50) and Korsemeyer and Peppas diffusion exponent (n) , were analyzed using the response surface methodology. The parameters were analyzed using the F test, and mathematical models were generated for each response parameter using multiple linear regression analysis (MLRA) and analysis of variance (ANOVA). The three formulation variables studied had a significant effect (P < 0.05) on the TFT, while the levels of HPMC K4M and citric acid significantly influenced drug release. To develop an optimized formulation, numerical optimization with a desirability approach was used, establishing restrictions on the dependent and independent variables. The optimized formulation showed a drug release of 82.37% during the TFT of 8.5h in zero-order mode and a t50 value of 5.30h. The experimental values ​​of TFT, t50 and Rel10 observed agreed with those predicted by the mathematical models, confirming the predictability of MLRA and ANOVA.