FORMULATION DEVELOPMENT OF VALSARTAN FLOATING TABLETS EMPLOYING A NEW MODIFIED STARCH – OPTIMIZATION BY 23 FACTORIAL DESIGN

The objective of the present study is optimization of valsartan floating tablet formulation by 23 factorial design. Floating tablets of valsartan (80 mg) were formulated employing Cross linked starch-urea, a new modified starch (50 %) as matrix forming polymer, sodium bicarbonate as gas generating agent and beeswax and starch acetate as floating enhancers. Valsartan is an orally active anti-hypertensive drug, majorly absorbed from stomach and upper small intestine. Formulation of sustained release floating tablets of valsartan is needed because of its poor oral bioavailability and short biological half-life. Valsartan floating tablets were formulated as per 23 factorial design and were evaluated. The individual effects of sodium bicarbonate (Factor A) and starch acetate (Factor C) and their combined effect (AC) on the floating lag time were significant (P < 0.05).Whereas the individual effect of bees wax (Factor B) and all other combined effects of the three factors involved were not significant in influencing floating lag time of the tablets. Formulations Fa, Fab, Fac and Fabc exhibited excellent floating over more than 12 h with a floating lag time in the range 12-40 seconds. Higher levels (20 %) of sodium bicarbonate gave shorter floating lag time. Valsartan release from the floating tablets prepared except formulation Fa was slow and spread over 12 h and dependent on the composition of the tablets. Drug release from formulation Fa was very rapid. Valsartan release from the floating tablets was by non-fickian diffusion mechanism in all the cases except Fa. In the case of formulation Fa that gave rapid release of drug fickian diffusion was the drug release mechanism. Optimization of valsartan floating tablet formulation was done taking floating lag time as the parameter for optimization. The polynomial equation describing the relationship between the response, Y and the variables, X1 , X 2 and X3 based on the observed data was found to be Y = 8.996 - 8.596 (X1) + 2.396 (X2) – 2.431 (X1 X2) + 0.561 (X3) - 0.521 (X1 X3) + 0.396 (X2 X3) - 0.271 (X1 X2 X3).Based on the polynomial equation developed, the optimized valsartan floating tablet formulation with a floating lag time of 20 seconds could be formulated employing sodium bicarbonate (160mg/tablet), beeswax (28mg/tablet) and starch acetate (10mg/tablet). The optimized formulation (Fopt) exhibited a floating time of 12-14 h with a lag time of 21 seconds fulfilling the target floating lag time set indicating validity of the optimization technique employed. Key words: Cross Linked starch Urea, Floating tablets, Valsartan, Optimization, Factorial design, Sustained release.