Abstract
Purpose: The purpose of the present study was to formulate and evaluate nanosuspension of Valsartan (VAL), a poorly water soluble and low bioavailable drug (solubility of 0.18mgmL(-1); 23% of oral bioavailability) with the aim of improving the aqueous solubility thus the bioavailability and consequently better anti-hypertensive activity.Methods: Valsartan nanosuspension (VAL-NS) was prepared using high-pressure homogenization followed by lyophilisation. The screening of homogenization factors influencing nanosuspension was done by 3-factorial, 3-level Box-Behnken statistical design. Model suggested the influential role of homogenization pressure and cycles on drug nanosizing. The optimized formulation containing Poloxamer(-1)88 (PXM 188) was homogenized for 2 cycles at 500 and 1000bar, followed by 5 cycles at 1500 bars.Results: The size analysis and transmission electron microscopy showed nanometric size range and uniform shape of the nanosuspension. The in vitro dissolution showed an enhanced release of VAL from nanosuspension (VAL-NS) compared to physical mixture with PXM 188. Pharmacodynamic results showed that, oral administration of VAL-NS significantly lowered (p0.001) blood pressure in comparison to non-homogenized VAL (VAL-Susp) in Wistar rat. The level of VAL in rat plasma treated with VAL-NS showed significant difference (p0.005) in C-max (1627.47112.05ngmL(-1)), T-max (2.00h) and AUC(024) (13279.2 +/- 589.426nghmL(-1)) compared to VAL-Susp that was found to be 1384.73 +/- 98.76ngmL(-1), 3.00h and 9416.24 +/- 218.48nghmL(-1) respectively. The lower T-max value, proved the enhanced dissolution rate of VAL.Conclusion: The overall results proved that newly developed VAL-NS increased the plasma bioavailability and pharmacodyanamic potential over the reference formulation containing crude VAL.