Optimization of Valsartan SR Floating Tablet Formulation by 22 Factorial Design and Multiple Regression Technique

The objective of the present study is optimization of valsartan SR floating tablet formulation by 22 factorial design. SR floating tablets of valsartan (80 mg) were formulated employing HPMCK100M (factor A) as matrix forming polymer, sodium bicarbonate (factor B) as gas generating agent and beeswax and ethyl cellulose 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 22 factorial design employing HPMCK100M (factor A) and sodium bicarbonate (factor B). The 2 levels of factor A are 20 and 60 % of the tablet weight and the 2 levels of factor B are 10 and 20% of the tablet weight. The Valsartan floating SR tablets were prepared by wet granulation method and were evaluated. Valsartan SR floating tablets prepared as per 22 factorial design were non-disintegrating in water and aqueous acidic (pH 1.2) and alkaline (pH 7.4) fluids and were of good quality with regard to drug content, hardness, friability and suitable for controlled release. The individual effect of sodium bicarbonate (factor B) and combined effect of HPMCK100M and sodium bicarbonate (AB) on the floating lag time are significant (P < 0.05). Formulations Fb and Fab exhibited excellent floating over >12 h with a floating lag time in the range 15-45 seconds. Higher levels (20 %) of sodium bicarbonate gave shorter floating lag time. Valsartan release from the floating tablets prepared was slow and spread over 12 h and dependent on the composition of the tablets. Valsartan release from the floating tablets prepared was by non-fickian diffusion mechanism in all the cases. Optimization of valsartan sustain release floating tablet formulation was done taking floating lag time as the parameter for optimization. For optimization, floating lag time was taken as response (Y) and level of HPMCK100M as (X1 ) and level of sodium bicarbonate as (X2 ). The polynomial equation describing the relationship between the response, Y and the variables, X1 and X2 based on the observed data obtained by multiple regression was found to be Y = 123.75 - 31.25 (X1) – 93.75 (X2) +16.25 (X1 X2). Based on the polynomial equation developed, the optimized valsartan sustain release floating tablet formulation with the desired floating lag time could be formulated employing HPMCK100M (200 mg/tablet) and sodium bicarbonate (101 mg/tablet). The optimized formulation (Fopt) exhibited a floating time of > 12 h with a lag time of 24 seconds and gave a release rate (K0 ) of 7.85 mg/hr fulfilling the target floating lag time set indicating validity of the optimization technique employed. The release rate (K0 ) of the optimized formulation (7.85 mg/hr) was very close to the desired release rate (K0 ) of Valsartan (7.4 mg/hr) based on its pharmacokinetics. The optimized formulation (Fopt) exhibited a slow release of Valsartan over 12h. As such, formulation Fopt is considered as the best floating tablet formulation of valsartan suitable for b.i.d administration