The Application of the Box-Behnken Design Response Surface Methodology to Study Optimized Formulation Variables on the Drug Release Pattern of Benidipine Hydrochloride Extended-release Matrix Tablet

Abstract

Background: In this research study, an attempt has been made using Box–Behnken design (BBD) Response Surface Methodology to find optimized formulation variables at their 3 levels (Low, medium and high) to affect the dependent response which is % drug release pattern at different time intervals in extending drug release of Benidipine Hydrochloride(BH) matrix tablets. BH extended release tablets reduce the side effects associated with multiple dosing used during conventional tablets. Methods: As in the preliminary work, we have found the most profound formulation factors for extending drug release of BH matrix tablets are Eudragit RS 100 amount (X1), HPMC K 100 M (X2), chitosan amount (X3), which we selected as independent factors at their low and high levels for this study considering % drug release at three different time intervals i.e. R1 (% of drug release in 2hr), R2 (% of drug release in 15hr) and R3 (% of drug release in 18hr) as dependent variables using dissolution media of phosphate buffer pH 6.8 with 75rpm. Results: From the experimental runs of prepared tablets as predicted by Design Expert software, the model shows a quadratic equation due to less p value, and a very less difference was observed between adjusted R2 and predicted values R2in all selected responses which we considered as % drug release. Conclusion: Thereforeby using the graphical response surface plot of BBD software,the optimized formulation of BH extended release tablet of Eudragit RS 100, HPMC K 100 M, Chitosan containing an amount of 45mg , 105 mg, and 45.71 mg respectively which shows an extended drug release of more than 18 hr. For constructing a satisfying fit of the model for the optimized formulation, result analysis was carried out for the internally studentized residuals versus the experimental runs indicating all data points are placed within the limits and the values of the predicted and actual response of each run were normally distributed near a straight line.