Development and Optimization of Pulsatile Release Formulation of Valsartan for Chronotherapy of Hypertension

The aim of present work was to develop pulsatile release dosage form for chronotherapy of hypertension. Considering the biopharmaceutical, pharmacodynamics reasons of Valsartan and circadian rhythm of hypertension a time controlled rupturable tablet, which allowed the release of Valsartan in time controlled release manner was developed for treating early in the morning surge of blood pressure. Core tablet for formulation were prepared using direct compression technique and evaluated for various parameters like % drug content, hardness, thickness, friability and In-vitro disintegration time. To get desired lag time and release profile to achieve pulsatile delivery tablets were coated with ethyl cellulose: Eudragit L100 (3:1), containing dibutyl phthalate and magnesium stearate. Coated tablet was evaluated for in vitro dissolution study, Drug content and rupture time. Optimization was done by using 32 full factorial design by using conc. of croscarmellose in core and coating level as independent variables and rupture time or lag time as dependent variable. Formulation F-5 was found to optimized formulation containing 5% of superdisintegrant in core tablet and 5 % coating level. From the study it is also concluded that Increase in coating level increases lag time & increase in concentration of superdisintegrant decreases lag time.