Nanosizing of valsartan by high pressure homogenization to produce dissolution enhanced nanosuspension: pharmacokinetics and pharmacodyanamic study |
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Authors: | Shayana Gora Gulam Mustafa Jasjeet Kaur Sahni Javed Ali |
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Institution: | Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi, India |
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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 0.18?mg?mL?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?188 (PXM 188) was homogenized for 2 cycles at 500 and 1000?bar, 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 (p?≤?0.001) 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 (p?≤?0.005) in Cmax (1627.47?±?112.05?ng?mL?1), Tmax (2.00?h) and AUC0→24 (13279.2?±?589.426?ng?h?mL?1) compared to VAL-Susp that was found to be 1384.73?±?98.76?ng?mL?1, 3.00?h and 9416.24?±?218.48?ng?h?mL?1 respectively. The lower Tmax 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. |
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Keywords: | Anti-hypertensive high-pressure homogenizer nanosizing particle size distribution scanning electron microscopy valsartan |
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