The Reach Of Preparation,Characterization And Bioavailability Of Two High Water-Soluble Taxifolin Powders

Taxifolin is a kind of biological flavonoid,has many important and useful bioactivities and pharmacological activities to humans owing to its special structxure.However,its low bioavailability is a major obstacle for biomedical applieations,so the experiment is designed to prepare taxifolin nanoparticles by the liquid antisolvent precipitation method,and inclusion complex of taxifolin-y-CD by the emulsion solvent evaporation and the freeze drying combination method to improve its bioavailability.In this paper,the main research works and results were as follows:This article applies the liquid antisolvent precipitation method to prepare successfully taxifolin nanoparticles,and proceeds in vivo and in vitro detections for taxifolin nanoparticles.The main contents and results are as follows:the experiment adopted the single factor experiment,and investigated primarily the concentration of poloxamer 188 as the surfactant,drug concentration,volume ratio of antisolvent to solvent,precipitation temperature,dropping speed,stirring speed,stirring time factors affecting drug particles size.The optimum conditions were:the poloxamer 188 concentration was 2.5 mg/mL,the drug concentration was 0.08 g/mL,the volume ratio of antisolvent to solvent was 10,the precipitation temperature was 25℃ the dropping speed was 4mL/min,the stirring speed was 800 r/min,the stirring time was 5 min.Taxifolin nanosuspension with a MPS of 24.6 nm were obtained under the optimum conditions.For getting taxifolin nanoparticles,the lyophilization method was chosen and correspondingly γ-cyclodextrin was selected as cryoprotectant from γ-cyclodextrin,mannitol,lactose,glucose.Then the properties of raw taxifolin and taxifolin nanoparticles were characterized by scanning electron microscopy(SEM),Fourier-transform infrared spectroscopy(FTIR),High performance liquid chromatography-mass spectrometry(LC-MS),X-ray diffraction(XRD),differential scanning calorimetry(DSC),and thermo gravimetric(TG),and the conclusion was drawn that taxifolin nanoparticles can be converted into an amorphous form but its chemical construction can,t been changed.Furthermore,dissolving capability test,2,2-diphenyl-1-picrylhydrazyl(DPPH)radical-scavenging activity and reducing power assay,solvent residue test were also carried out.The experimental datas showed that the residual ethanol of the taxifolin nanoparticles was less than the ICH limit for class 3 solvents of 5000 ppm or 0.5%for solvents;The antioxidant capacity of taxifolin nanoparticles was superior to raw taxifolin;The solubility and the dissolution rate of taxifolin nanoparticles were about 1.72 times and 2.84 times of raw taxifolin;The bioavailability of taxifolin nanopartieles increased 7 times eompared with raw taxifolin.This study selected y-cyclodextrin(γ-CD)as the inclusion material and prepared inclusion complex of taxifolin-γ-CD by the emulsion solvent evaporation and the freeze drying combination method to achieve the improvement of the solubility and oral bioavailability of taxifolin.We selected ethyl acetate as the oil phase,deionized water as the water phase.The taxifolin emulsion was prepared using adjustable speed homogenate machine in the process of this experiment,whose particle size was related to the concentration of taxifolin solution,the volume ratio of water phase to oil phase,the speed and time of homogenate.We knew through the single-factor test that,the optimum eonditions were:the coneentration of taxifolin solution was 40 mg/mL,the volume ratio of water phase to oil phase was 1.5,the speed of homogenate was 5000 rpm,the homogenate time was 11 min.Taxifolin emulsion with a MPS of 142.5 nm was obtained under the optimum conditions,then the high-concentration taxifolin solution(3 mg/mL)was obtained by the rotary evaporation process.Finally,the inclusion complex of taxifolin-γ-CD was prepared by vacuum freeze-dry.The characteristics of the inclusion complex of taxifolin-γ-CD were analyzed using SEM,FTIR,XRD,DSC,and TG The FTIR results analyzed the interaction of taxifolin and γ-CD and determined the molecular structure of the inclusion complex of taxifolin-γ-CD.The analysis results of XRD,DSC and TG indicated that the inclusion complex of taxifolin-γ-CD was obtained and showed significantly different characteristics with taxifolin.In addition,dissolving capability test,antioxidant capacity test,solvent residue test were also carried out.The experimental datas showed that the amounts of residual solvent of the inclusion complex of taxifolin-γ-CD was less than the ICH limit for class 3 solvents of 5000 ppm or 0.5%;The antioxidant capacity of inclusion complex of taxifolin-γ-CD was superior to raw taxifolin;The solubility of inclusion complex of taxifolin-γ-CD was about 18.5 times of raw taxifolin;The dissolution rate of inclusion complex of taxifolin-γ-CD were about 3 times of raw taxifolin;The bioavailability of inclusion complex of taxifolin-γ-CD increased 3.72 times compared with raw taxifolin.These results suggested that the taxifolin nanoparticles and the inclusion complex of taxifolin-γ-CD may have potential value to become a new oral taxifolin formulation with high solubility.In addition,in this paper,two kinds of water-soluble powder are also compared and analyzed in purity,solubility and bioavailability and so on,the conclusion obtained is that the solubility and dissolution rate of the inclusion complex of taxifolin-γ-CD is superior to the taxifolin nanoparticles,and the purity and oral bioavailability of taxifolin nanoparticles are better than inclusion complex of taxifolin-γ-CD.So,they have their own advantages and both have great reference value and application value.