Study On Silymarin Nanosuspension And It’s Solidification

Silymarin is the effective fractions extracted from milk thistle seeds in Compositae with antioxidant and anti-fibrosis,anti-inflammatory,anti-tumor,immune regulation effect and so on.However,due to its low water solubility and poor bioavailability,the impact of clinical efficacy is affected.Silymarin nanosuspension was prepared to improve drug dissolution in vitro in this paper.At the same time,in order to improve instability of liquid preparation,the nanosuspension was further solidified by fluidized bed spray drying.Finally,physicochemical properties and preliminary quality evaluation of solid preparation was investigated.The main results and conclusions are as follows:Analysis method of silymarin and silybin in vitro was established.TLC method was used to qualitatively identify drug substance of silymarin.Determination of silymarin in raw materials by UV method,determination of silybin by HPLC method.With silymarin as quantitative indicators,in vitro release of measurement method was established.The above analysis methods lay the foundation for process research and preliminary quality evaluation of molding preparation.Silymarin nanosuspension was prepared by solvent precipitation method combined with high pressure homogenization method.The best stabilizer was povidone K30 and sodium dodecyl sulfate.The optimal process was as follows:injection rate of oil phase was 15 mL/min,mixing rate of water phase was 800 r/min,precipitation temperature was 0 ℃,homogenization pressure was 100 MPa,and number of homogenization was 12 times.The optimal formulation was as follows: the concentrations of silymarin,povidone K30 and sodium dodecyl sulfate were 4,1.3and 0.7 g/L,respectively.The average particle size of silymarin nanosuspension was(191.4 ± 1.4)nm,and polydispersity index(PDI)was 0.135 ± 0.003(n=3).At 60 min,the accumulative release rate of silymarin nanosuspension was 94.02%,while that of silymarin was only 34.07%.Therefore,Preparing silymarin nanosuspensions can effectively improve its dissolution.Silymarin nanosuspension was further solidified by fluidized bed spray drying.Silymarin nanocrystalline pellets was prepared.The technology parameters were thus optimized,viz.,the blowing frequency was 18 Hz,the fluidization temperature was 38—42 ℃,the hydroxypropyl methylcellulose E5 consumption was 0.16%,the speed of constant flow pump was 9.5 r /min,and atomization pressure was 0.12 MPa.Silymarin nanocrystalline pellets was uniform,smooth,plump and yellow.The yield of Silymarin nanocrystalline pellets was(85.74 ± 1.29)%,layering efficiency was(86.43 ± 1.52)%,average particle size of redispersion was(251.6 ± 3.8)nm,and PDI was 0.184 ± 0.015(n=3).Physicochemical properties of silymarin nanocrystalline pellets were investigated.Redispersion properties results showed that the average particle size and PDI of silymarin nanocrystal pellets were increased.But,the average particle size was less than 300 nm,PDI was less than 0.2,which showed that silymarin nanocrystal pellets keep good redispersion properties.Chemical structure of drug did not change in silymarin nanocrystalline pellets through the analysis of UV and infrared spectroscopy(FT-IR).Silymarin was dispersed in carrier with an amorphous or molecular state through the analysis of differential scanning calorimetry(DSC)and X-ray diffraction(XRD).In vitro dissolution test showed that,cumulative release rate of silymarin nanocrystalline pellets reached more than 90% at 30 min.Nevertheless,cumulative release rate of silymarin was only 34.87% at 60 min.There was no difference in dissolution between silymarin nanocrystalline pellets and silymarin nanosuspension,which showed that the combination of nanosuspension and fluidized bed spray drying is an effective way for improving dissolution of silymarin and stability of preparation.Preliminary quality of silymarin nanocrystalline pellets was evaluated.The qualitative and quantitative analysis method of silymarin nanocrystalline pellets was determined.In vitro dissolution of silymarin nanocrystalline pellets release fastly and stablely.Influence factor test results showed that silymarin nanocrystalline pellets were stable in strong light and high heat.The character,redispersion properties,silymarin content and dissolution of them were not significantly changed.However,Under high humidity condition,they were easy to absorb moisture,which prompted they should be kept in a dry environment.