Preparation Of Silibinin Super-saturated Self-nanoemulsion And Its Evaluation

Purpose: In this paper,we use the supersaturated nano-microemulsion delivery system to improve the solubility of the water-insoluble drug silybin,and to improve the antioxidant biological activities.Methods: The oil phase,emulsifier and emulsifier were screened by measuring the solubility of silybin in the three media and emulsifying effect.The pseudo-ternary phase diagram was drawn and the size of the milk area was compared to determine the composition of the prescription.The particle size,PDI,Zeta potential and self-determination,the emulsification time,and light transmittance,etc.are optimized for the evaluation index,and the drug loading is determined.Functional oils were screened by combining DPPH free radical scavenging and potassium ferricyanide reduction capacity,and the composition of oil phase was further optimized.The ingredients for promoting supersaturation were screened by dissolution degree,and the prescription composition was finally determined.The content,stability,in vitro dissolution,antioxidant capacity and cytotoxicity of silybin S-SNEDDS were evaluated.Results: The formulation of silybin S-SNEDDS was:(1)wheat germ oil/Capryol 90-Cremophor ELP-Transcutol HP-Soluplus;(2)seabuckthorn seed oil/Capryol 90-Cremophor ELP-Transcutol HP-Soluplus;Wheat germ oil/Capryol 90-Cremophor RH40-Transcutol HP-Soluplus;(4)Seabuckthorn seed oil/Capryol 90-Cremophor RH40-Transcutol HP-Soluplus;drug loadings were 0.87%,0.87%,1.835%,2.116%,respectively The color of the silybin S-SNEDDS is light yellow transparent or bright yellow transparent,and the texture is uniform.The TEM presents a nearly spherical white emulsion.After self-emulsified and dispersed,the dispersed emulsion is a light blue opalescent or clear transparent dispersion emulsion with an average particle size of 20 ~ 50 nm,a potential value of-9.547 ~-30.833 m V,a light transmittance over 95%,and an emulsification time of 45 s ~ 65 s.The content of the drug in the wheat germ oil/Capryol 90-Cremophor ELP-Transcutol HP-Soluplus system is 8.955 ± 0.040 mg/g,and the drug content is 8.872 ± 0.068 mg in the seabuckthorn seed oil/Capryol 90-Cremophor ELP-Transcutol HP-Soluplus system.The in vitro dissolution rate of silybin S-SNEDDS can reach more than 90% within 8 h.Under the conditions of light,dark,4 ° C,25 ° C for 10 days,silybin S-SNEDDS exhibited good stability.When the concentration of silybin was 200 ~ 400 μg/ml,the S-SNEDDS free radical scavenging rate of silybin was 25.370% ~ 94.222%,which was higher than the free radical scavenging rate of silybin raw materials at the same concentration(23.302% ~ 62.901%);when the concentration of silybin is 130 ~ 280 μg/ml,the absorbance of silybin S-SNEDDS and potassium ferricyanide is between 0.452 and 0.782,which are higher than the same concentration of silibinin.The absorbance of the guest material(0.411 ~ 0.760);the above indicates that the anti-oxidation effect of the silybin S-SNEDDS system is stronger than that of the silybin.Silibinin S-SNEDDS is less toxic to human colon cancer Caco-2 cells.Conclusion: Silibinin S-SNEDDS was successfully prepared,and the in vitro dissolution and antioxidative activity of silybin was improved,and with good safety.It was applied to improve the poor solubility of drug by supersaturated nano-microemulsion delivery system,and provide the design of oral delivery system for traditional Chinese medicine ingredients.