Research On The Baicalin Nanosuspensions

Baicalin is a flavonoid extracted from dried roots of scutellaria baicalensis Georigi. Baicalin is composed of baicalein and a molecular glucuronide glycoside compound formation,which exist in the scutellaria baicalensis georigi.Baicalin has a variety of pharmacological effects, such as antihypertensive,anti-bacterial,anti-inflammatory effects and so on.Baicalin can be absorbed into the blood after scutellarein by enzymatic hydrolysis in the gut, quickly transformed into baicalin in vivo. However,poor solubility (<0.1mg·mL-1) and stability (decomposition under alkaline conditions), greatly limits its widespread application in clinical practice. In recent years, more relevant reports are focused new technologies and new formulations to increase the solubility of baicalin, extensive research were carried out on β-cyclodextrin inclusion complexes, solid dispersion, phospholipid complex, microparticles, nanoparticles, liposomes, nanoemulsions,metal complexes and other technologies.This paper is aim to screen the best preparation of nano-suspension of baicalin by a single factor test, using carrier-nanometer suspension technology (carrier-free nanosuspensions),using the new manufacturing techniques for preparing microcrystalline baicalin nanosuspension (baicalin nanosuspensions), with particle size and polydispersity (polydispersity index, PDI) as an indicator.In this experiment, several indexes on the nanosuspension were investigated, such as particle size, morphology, solvents, stabilizer, operating temperature to prepare the best formation. In order to improve the storage stability of freeze-dried powder of baicalin nanosuspension was made, the effects of saturation solubility of baicalin nanocrystals lyophilized powder, in vitro dissolution and storage stability were investigated. Structure analysis of baicalin nanocrystals was performed by XRD technique. The concentration of baicalin was determined by HPLC-MS/MS via the tail vein injection in plasma of rats. DAS2.0pharmacokinetic software was used to calculate the pharmacokinetic parameters.Baicalin was dissolved in dimethyl sulfoxide solution dubbed50g· L-1, and injected20times the amount of0.5%aqueous solution of lecithin, and then by high-speed cutting under ice-water bath,centrifuge30OOOr· min-1for8min.So the nano suspensions was spherical and PDI was lower, which was placed at room temperature for30days, and the suspension particle size increases rapidly, but the particle size of freeze-dried powder did not change. It was showed that the solubility of nano-crystalline improved1.64times than the original drug baicalin;Significantly different on the plasma concentration-time curves was found by the Kinetic studies in rats on baicalin solution and baicalin nanosuspensions. After intravenous injection of baicalin solution, pharmacokinetic parameters of the rats were obtained:AUC=5687.1ug·L-1· h, MRT=1.911h, CLz=2.67L· h-1· kg-1; After intravenous injection of baicalin nanosuspensions, AUC was significantly higher in vivo significantly,the mean residence time (MRT) was longer, and the clearance rate was significantly decreased, AUC=6824.0ug· L-1· h, MRT=2.681h, CLz=1.84L· h-1· kg-1,respectively.Experimental results shown that the preparation of nanosuspensions can significantly improve solubility of baicalin, in vivo pharmacokinetic studies have shown that duration time and AUC of baicalin nanosuspensions in the body was prolonged and increased compared with baicalin solution.In a word, bioavailability of baicalin was greatly improved by nanosuspension some extent.