Title: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
Volume: 12
Issue: 1
Author(s): Amaresh Prusty*, Bijon K. Gupta and Amiyakanta Mishra
Affiliation:
- Department of Pharmaceutics, College of Pharmaceutical Sciences, Puri Odisha, India
Keywords:
Box Behnken Design (BBD), Benidipine Hydrochloride (BH), Matrix Tablet, ANOVA, QbD, Eudragit.
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 3 levels
(low, medium, and high) to affect the dependent response, which is the % 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 of 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
2 hours), R2 (% of drug release in 15 hours) and R3 (% of drug release in 18 hours) as dependent
variables using a dissolution media of phosphate buffer pH of 6.8 with 75rpm.
Results: From the experimental runs of prepared tablets as predicted by the 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 R2
in all selected responses, which we considered as the
% drug release.
Conclusion: Therefore, by 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, and Chitosan
containing an amount of 45mg, 105 mg, and 45.71 mg, respectively shows an extended drug
release of more than 18 hours. To construct a satisfying fit of the model for the optimized formulation,
a result analysis was carried out for the internally studentized residuals versus the experimental
runs indicating all data points were placed within limits, and the values of the predicted and actual
response of each run were normally distributed near a straight line.
