Effect of Recrystallization Technique on Oral Bioavailability of Valsartan

Abstract

Valsartan (VAL) is a widely prescribed anti-hypertensive agent with angiotensin II type I receptor antagonistic activity. VAL belongs to BCS class II having a low and variable oral bioavailability (10-35%) and its absorption is dissolution rate limited. Recrystallization of VAL from different organic solvents improved VAL aqueous solubility and thereby in vitro dissolution properties. In this investigation in vivo oral bioavailability (BA) of VAL and its recrystallized products with methanol and ethanol (VMET and VETH respectively) solvents was evaluated in male Wistar rats. Also, a rapid, economical and reliable RP-HPLC-PDA method was developed for the estimation of VAL in rat plasma samples and validated according to ICH guidelines. Chromatographic separation was achieved on an Agilent eclipse C18 column (150×4.6mm, 5µ) with a mobile phase composition of 10mM ammonium acetate: acetonitrile (75:25%v/v) at a flow rate of 1.2 mL/min. The retention time of VAL was found to be 2.9 min and showed good linearity (R2>0.996) in the selected concentration range of 0.5-25µg/mL. A 2.9, 2.8 folds increase in Cmax and a relative bioavailability of 320, 305% was observed with VMET and VETH respectively, when compared to that of untreated VAL. Thus it can be inferred that recrystallization is easy and economical technique for enhancing the pharmaceutical properties like solubility, dissolution properties and oral BA of poorly water soluble drugs like VAL. Keywords: Bioanalytical method, Bioavailability, Male Wistar rats, Valsartan, Recrystallization