Study On Preparation And Pharmaceutical Characteristics Of Naringenin Nanocrystals

Naringenin is a dihydrogen flavonoid which exists in many natural plants such as grapes,grapefruit,lemon,grapefruit.It has a variety of pharmacological functions,such as anti-inflammatory,anti-cancer,anti-oxidation,and anti-fibrosi.But the bioavailability of naringenin is influenced due to the poor solubility of drug.The clinical application of naringenin is limited.In this paper,starting from increasing the solubility of the drug,naringenin nanocrystals were prepared by drug nanocrystal technology,with the expectation of increasing the solubility and dissolution,and improving the drug absorption and bioavailability via reducing particle size of the drug.The UV and HPLC methods were established respectively in this paper for the analysis of the solubility and dissolution and the assay of naringenin.The results showed that the methods were accurate,reliable,stable,and applicable to the quality control of the naringenin nanocrystals.Naringenin nanocrystals were prepared by media grinding in this paper.The technological conditions of this method were studied with particle size and Polydispersity index（PDI）as examining index.The process parameters,such as drug concentrations,types and concentrations of stabilizer,machine rotating speed,grinding time,the amount and size of the grinding media,were investigated via single factor test.Furthermore,the process conditions were optimized in an orthogonal test of four factors and three levels and liquid naringenin nanocrystals were solidified by spray drying technology.The problem of secondary agglomeration of particles was solved in this process,the optimized process parameters were as follows:the concentration of drug was 200 mg/m L,the concentration of stabilizer（PVPK30）was 8wt%,the concentration of dispersant（PEG）was0.3wt%,the amount of milling pearls was 8.0 g,and the time of grind was 3 h.In this paper,the pharmacological properties of naringenin nanocrystals were studied,including particle size distribution,morphology,crystalline state,chemical structure,solubility and dissolution.The results showed that the home-made nanocrystals were irregular massive crystals,the average particle size was（400.7±6.9）nm,and the particle was uniform.After nanocrystallization,no significant changes have been observed in crystalline state and chemical structure of naringenin.The solubility and dissolution of nanocrystals were improved.The experimental animals were Wistar rats（male）.HPLC was employed to determine the naringenin concentration in plasma.The results showed that the methods were accurate,reliable,stable,and applicable to determine the naringenin concentration in plasma.Pharmacokinetics of the home-made nanocrystals were studied by single dose test with naringenin physical mixtures as contorl.The results were as follows:after oral administration of the physical mixtures and the nanocrystals,the peak concentration of naringenin(C_max)in plasma were（214.10±34.10）ng/m L and（373.75±64.07）ng/m L,respectively.The peak time(T_max)were 1 h.The area under plasma drug concentration-time curve(AUC_0-∞)were（1226±157.74）ng?h/m L and（2237±296.88）ng?h/m L,respectively.The results indicated that naringenin nanocrystals could improve drug absorption and bioavailability.The relative bioavailability was 182.5%.