The Study Of Sophoraflavanone G Solid Self-microemulsion Drug Delivery System

Sophoraflavanone G is for leguminous plants of the sophora flavescens Ait isopentenyl flavonoids two hydrogen.The content of total flavonoids in the total flavonoids was higher.Pharmacological studies show that SFG has a variety of pharmacological activities,such as anti-bacterial,anti-tumor,anti-inflammatory,anti malaria,nervous system protection and the potential of skin whitening effect.However,does the SFG side chain of the lavandulyl structure affect the water solubility of the compound and further affect its oral absorption and its effect.Based on this,this study on SFG study physicochemical properties and biological properties of the proposed to improve the oral bioavailability of SFG by self emulsifying drug delivery system technology.Specific,carried out the following five aspects of research.1.Isolation and structure identification of SFGFirst of all,using ethyl acetate as the solvent,preparation of total flavone extract by ultrasonic method.Secondly,the light yellow powder was obtained by the method of silica gel column chromatography and ODS reverse phase column chromatography.The powder by UV,IR,NMR,and reported in the literature(2S)-Lavender based-5,7,2’,4’-hydroxy dihydro flavonoids data control,consistent and determined the structure of SFG.2.The study of SFG prescription2.1 The Study of physical and chemical properties of SFGThe HPLC method was used to establish a quantitative analysis method of SFG,with C18 Dikma as the column and methanol water as mobile phase,the detection wavelength was 296nm.The study showed that the linear relationship of SFG was good,and the recovery rate,precision,repeatability and stability of RSD were less than 2%.The solubility,oil-water partition coefficient and pKa value of SFG were investigated by using SFG as an index.According to the 2015 edition of "Pharmacopoeia" provisions of the Chinese,SFG belongs to soluble drugs.SFG in oil-water partition coefficient of ph1.2,5.8,6.8 and 7.0 and 7.2 respectively 1.21 ±0.04、1.25±0.09、1.61 ±0.07、1.54±0.15、1.50±0.12,SFG under different pH conditions in the oil/water partition coefficient were greater than 1,show that the SFG fat better solubility.The pKa value of SFG under different pH was 7.15±0.44.2.2 Study on pharmacokinetics of SFG in ratsThe UPLC-MS/MS analysis method of SFG in plasma samples was established with SD rats as experimental animals.Using ACQUITYUPLC?HSS T3 C18 column,acetonitrile and 0.1%formic acid water as mobile phase in gradient elution,flow rate of 0.2mL/min until measured the plasma samples were prepared with acetic acid ethyl ester liquid liquid extraction.MS/MS uses electrospray ionization source(ESI)and multiple reaction monitoring(MRM),negative ion detection mode,rutin as internal standard m/z was 423.2→161.2(SFG)and 609.3→300.3(Rutin).The results showed that SFG had good linear relationship within the concentration range of ng/mL 0.08～160 ng/mL(R2=0.9975)The precision and stability of RSD were less than 15%,and the recovery rate was between 79.6%～83‘5%.Vein to drug T1/2z is 0.169h and AUC0→∞ is 271.031 μg×h/mL,MRT0→∞ is 4.784h;T1/2z is 1.903h,Tmax is 2.167h,AUC0→∞ is 492.909μg×h/mL,MRT0→∞ is 11.417h;SFG in rats of the absolute biological utilization degree F=10.3%and its bioavailability is low.3.Study on drug delivery system of SFG-SMEDDSThe saturated solubility of determination of SFG in different materials,and compatibility test of oil phase,emulsifier,and drawing method of ternary phase diagram.Excluding SFG solubility relatively small accessories,to emulsify efficiency is highest level,the formation of self emulsifying area size index,the final SFG-SMEDDS prescription composition with ethyl Oleate-Cremphor RH40-PEG400 system formed maximum self microemulsion area.The prescription oil phase of SFG-SMEDDS was determined as Oleate Cremphor,emulsifier as RH40 Ethyl,and auxiliary emulsifier as PEG-400.Single factor experiment with particle size as indexes examines the formulation factors of oil phase,emulsifier and auxiliary emulsifier,drug dosage of SFG self microemulsion,to determine the various accessories to join the proportion of range and drug join the SFG-SMEDDS no effect.On the basis of self microemulsion system,the particle diameter,emulsification time and loading as the prescription evaluation of the dependent variable,through D-optimal mixed experimental design of optimized the best ratio of each component,formulation optimization,Ethyl Oleate 38.5%,Cremophor RH4047.5%,PEG-400 14.0%,drug loading 20mg/g.Single factor was used to investigate the effect of dilution ratio,temperature,stirring speed and emulsifying medium.The results of SFG-SMEDDS,37 degrees of temperature,stirring speed 50r/min,and no influence on self microemulsion.Finally,the preparation process of SFG-SMEDDS was determined.4.Study on Preparation and preliminary stability of SFG-S-SMEDDSInvestigation of solid adsorption material,SFG-SMEDDS adsorption,the formation of solid particles.Through the comparison of the adsorption capacity and the influence of the solid adsorption material on the emulsification efficiency,the mannitol was determined as the solid adsorption material,the mass adsorption ratio of SFG-SMEDDS and mannitol was 1:2,and the SFG-S-SMEDDS was prepared.SFG-S-SMEDDS after the dispersion of the particle size of 38.5±1.0nm emulsifying time for 34.6±1.4s and potential for-39.1±1.8mV,the solution presented light blue milk.The system by SFG-S-SMEDDS under transmission electron microscope(TEM)uniform ball of solid particles and uniform distribution.The cumulative release percentage of SFG-S-SMEDDS and SFG in vitro was determined by the dissolution test method and the SFG content as the index.The results showed that the dissolution rate of SFG-S-SMEDDS in the former 10min reached 50%,30min reached 80%,far greater than the SFG it self,in vitro experiments showed that SFG made of solid self microemulsion,can effectively improve the dissolution rate.5.Study on relative bioavailability of SFG-SMEDDSThe pharmacokinetics of SFG-SMEDDS in rats were studied by using UPLC-MS/MS technique.The results showed that compared with CMC-Na suspension liquid,SFG-SMEDDS medicine under the curve area significantly greater than CMC suspension liquid itself,after oral administration of SFG self microemulsion afterT1/2z is 3.200h and Tmax for 0.792h,AUC0→∞ is 652.977μg×h/mL,MRT0→∞ is 11.278h;SFG in rats in vivo relative biological use of about 343.84%that SFG made since the microemulsion can effectively improve the biological utilization degree.