Nanosuspensions technique is an important tool to enhance the saturation solubility and dissolution velocity of poorly soluble drugs. Trans-resveratrol (t-Res) with extensive pharmacological effects was severely restricted by poor solubility and short biological half-life. In this study, anti-solvent precipitation was employed to development trans-resveratrol nanosuspensions (t-Res NS) with PVPK30 as stabilizer. The physicochemical properties, in vitro release and in vivo pharmacokinetics of t-Res NS were investigated. The mean particle size, zeta potential, encapsulation efficiency and drug loading of t-Res NS prepared by the optimal prescription were 96.9 nm, -20.4mV, 78% and 28.1%, respectively. The morphology of t-Res nanoparticles was spherical indicated by SEM with amorphous phase verified by XRD and DSC. The t-Res NS present a good physical stability as well as enhanced chemical stability. Compared to crude drug, the in vitro dissolution rate of t-Res NS was increased with fitting Higuchi equation (Q=0.3215t1/2+0.0070). The in vivo pharmacokinetic test in rats showed that the AUC0∼t of t-Res NS (559.4 μg/mL·min) was about 3.6-fold higher than that of t-Res solution. Meanwhile, the MRT of t-Res nanosuspensions was longer than that of t-Res solution. These results suggested that NS may be a potentially nanocarrier for clinical delivery of t-Res.
Keywords: Nanosuspensions; anti-solvent precipitation; in vitro dissolution; in vivo pharmacokinetics; trans-resveratrol.