Formulation and optimization of gastric floating matrix tablets of Gatifloxacinwith combination of polymers using Box-Behnken experimental design

摘要

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing gatifloxacin as a model drug using Box-Behnken design. A 3-factor, 3-level Box-Behnken design was used to derive a second order polynomial equation and construct contour plots to predict responses. The independent variables selected were conc. of compritol ATO 888 (X1), conc. of poloxamer 188 (X2) and conc. of chitosan (X3). Batches were prepared by wet granulation method and evaluated for Floating lag time (FLT), Total floating time (TFT) and time required to release 50% of the drug (t50) as dependent variables. Compritol ATO 888 containing tablets were found to be significant for floating properties. Poloxamer 188 had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of chitosan on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties. The transformed values of the independent variables and dependent variables were subjected to multiple regressions to establish a full-model second-order polynomial equation. Contour plots as well as response surface plots were constructed to show the effects of X1, X2 and X3 on the FLT, TFT and t50. A model was validated for accurate prediction of the FLT, TFT and t50 by performing checkpoint analysis. The computer optimization process, contour plots and response surface plots predicted at the conc. of independent variables X1, X2, and X3 (25.25 %, 13.62% and 15% respectively), for maximized response of TFT. The Box-Behnken design demonstrated the role of the derived equation and contour plots with response surface plots in predicting the values of dependent variables for the preparation and optimization of gatifloxacin gastric floating matrix tablet.