Study On Nano-crystalline Suspension Of Quercetin

Quercetin, a plant flavonoid component, has a variety of pharmacological activities such as dilating coronary artery, decreasing blood lipid, analgesia, anti-platelet aggregation, anti-diabetic, anti-oxidation, anti-inflammation, anti-virus and anti-cancer and extremely low side-effects, thus it has a good study value and a widely promise in market. However, quercetin is poorly soluble in water and slightly soluble in oil, which results in the low oral bioavailability and limits the application in clinic. Nanocrystal suspension (NS) is a colloid system that consists of only pure drug crystal and minimum surfactant and/or polymer for stabilization. The system can carry more drug and increase the solubility and dissolution of poorly water-soluble drugs. It can improve the bioavailability when it is applied to intravascular administration routes such as oral, transdermal delivery. In this study, NS loading a model drug quercetin was prepared and the oral pharmacokinetics was investigated in rats.In this study, a tandem of nano-precipitation and high pressure homogenization method was used to prepare quercetin loaded NS. With the stability of quercetin loaded NS as the index, the stabilizers were screened, the preparation techniques were optimized and the freeze-dried procedures were investigated. The optimal quercetin loaded NS presented spherically shaped, uniform size and un-adhesion under transmission electron microscope. The mean particle size was 393.5 nm and the zeta potential was -35.75 mV. The solubility was significantly increased by NS about 70-fold compared to the crude drug. X-ray diffractometry (XRD) results indicated that the crystalline state of quercetin in nanosuspension did not change in the preparation.In the oral pharmacokinetics study, HPLC method was used to determine the concentration of quercetin in rat plasma. The pharmacokinetics parameters of rats administrated quercetin loaded NS showed that elimination rate constant decreased obviously and the mean residence time was longer. The AUC of NS loaded quercetin was increased 14-fold in comparison to the crude quercetin suspension, which showed that NS could markedly improve the oral bioavailability of quercetin. In this study, it can be proven that NS can increase the solubility of poorly water-soluble drugs and improve their oral bioavailability. It represents a promising new drug formulation for poorly water-soluble drugs.