Study On Licorice Flavonoids Preparation Based On Nanosuspension Technology

Glycyrrhiza flavonoids is a kind of fat-soluble substance with strong physiological activity extracted from licorice root and rhizomes.It has the functions of lowering blood glucose,lowering blood fat,anti-tumor,liver protection,anti-inflammatory and anti-ulcer,however due to its poor water solubility and low bioavalability,it has severely limited clinical application and development.In this paper,the flavonoid nanosuspension of licorice was prepared based on nanosuspension technology.The lyophilized flavonoid nanosuspension was solidified by freeze-drying method.The lyophilized powder was used as raw materials to further prepare capsules and evaluate their quality.To increase the solubility and dissolution of licorice flavonoids and improve the stability of the preparations.The main research content is as follows:First of all,the in vitro analysis method of licorice flavonoids was established.TLC method was used to qualitatively identify drug substance of the licorice flavonoids.The UV method was used to determine the content of licorice flavonoids in the drug substance and HPLC method was used to determine the content of glycyrrhizin.And the dissolution of flavonoids in licorice from different media was investigated and a method for the determination of in vitro release was established.The above analysis methods provide the basis for subsequent formulation research and preliminary quality assessment.Precipitation-high pressure homogenization method was adopted in the preparation of nanosuspensions.The best stabilizer was povidone K30?PVP K30?and polyethylene glycol 400?PEG-400?.The optimal process was as follows:the volumetric ratio of absolute ethanol to water is 1:10,the magnetic stirring speed is800 r/min,the cycle is firstly cycled under 50 MPa three times,and then cycled under120 MPa 15 times.The optimal conditions were determined to be 10.00 mg·mL^-1for flavonoids'concentration,and 2.30 mg·mL^-1for both PVPK30 and PEG-400concentrations.The appearance of the licorice flavonoid nanosuspension was all brown brownish solution with opalescence.The average particle size was?172.3±1.2?nm,and the polydispersity index was 0.175±0.004.The results showed that the licorice flavonoid nanosuspension The average particle size is small and the distribution is narrow and uniform.Freeze-drying method was used to solidify licorice flavonoid nanosuspension into lyophilized powder.The best lyoprotectant was 5%mannitol-lactose?3:2?.The average drug loading of lyophilized powder was?30.1±0.3?%,licorice flavonoid nanosuspension freeze-dried powder 60 min dissolution rate of 88.32%,while the raw material does not exceed 30%,indicating that licorice flavonoid nanosuspension freeze-dried powder can improve the dissolution of licorice flavonoids.The physicochemicalpropertiesof licorice flavonoidnanosuspension freeze-dried powders were investigated and their initial stability was investigated by UV spectrophotometry?UV?,Fourier transform infrared spectroscopy?FT-IR?and X-ray diffraction?XRD?.Analysis showed that the crystal form and structure of licorice flavonoids did not change during the process of preparation and freeze-drying,and they were always present in amorphous form,which was conducive to maintaining the biological activity of licorice flavonoids.The influencing factors test showed that the lyophilized powder has good stability under the conditions of high temperature 60°C,relative humidity 75%,strong light irradiation 4500lx±500lx,and can further prepare solid preparations of licorice flavonoids,so as to provide reference for expanding application of licorice flavonoids.Capsules were prepared from licorice flavonoid nanosuspension lyophilized powder as an intermediate.The best formulation for screening was licorice flavonoid nanosuspension freeze-dried powder 99.7%and talc 0.3%.The preliminary quality study of licorice flavonoids nanosuspension capsules was carried out.The qualitative and quantitative determination method of licorice flavonoid nanosuspension freeze-dried powder capsules was determined.Inspected capsule inspection requirements for items such as filling volume,moisture,and disintegration time limit.The results showed that the prepared lyophilized powder capsules were all in accordance with the regulations,and the content was uniform,the quality was stable,the dissolution was significantly improved,and the in vitro release rate of the batches was reproducible.The influencing factors of licorice flavonoids nanosuspension freeze-dried powder capsules were investigated.The results showed that the freeze-dried powder capsules were relatively stable to light,heat,and humidity.In summary,the nanosuspension technology can significantly improve the dissolution of licorice flavonoids,freeze-dried into lyophilized powder,to prepare freeze-dried powder capsules,its quality is stable,can significantly improve the drug dissolution and formulation stability.To expand the scope of application of licorice flavonoids to provide reference.It is suggested that nanosuspension technology can effectively solve the problem of low solubility and low bioavailability of insoluble components of traditional Chinese medicines.At the same time,this topic also provides experimental demonstrations for the research of nanosuspensions and their curing agents.