Studies On Preparation Process Of Vitexin Nanosuspension And Its Lyophilized Powders

The vitexin is a natural active ingredients flavonoids carbon anhydride.It has myocardial ischemia,lower blood pressure,anti-viral,anti-diabetic anti-tumor,anti-inflammatory analgesic,anti-oxidation and other biological activities and pharmacological effects.It is mainly used in clinical treatment of various cardiovascular diseases.However,due to its poor water-soluble,low solubility,resulting in low oral bioavailability,which severely limits its clinical application.Nano-suspension is a new drug delivery system by the end of the 20th century,and achieved fruitful results in the clinical applications of the insoluble drugs.Nanosuspension Is a drug nanoparticles rely on a small amount of surfactant to provide a stabilizing effect on the formation of a stable colloidal solution.The nano-suspension can effectively improve the solubility and dissolution of poorly soluble drugs to achieve the purpose of improving the bioavailability and therapeutic effect.In addition,it can achieve a controlled release drug delivery,targeting the role of the administration.Currently,many nano-suspensions can also be made into capsules,tablets,and other formulations to meet the needs of different diseases by solid,which improved its stability making it a broad clinical space to play.In this paper,the vitexin was made into nano-suspension by insoluble drug solubilization technology and then made into freeze-dried powder.The preparation and freeze-drying process of vetixin nano-suspension and its freeze-dried powder was established and determination of its physical and chemical properties.The intravenous injection iso vitexin nano-suspension by plasma concentration was determined.In addition,the stability of vitexin in artificial gastric juice and artificial intestinal fluid was studied,and the possibility of nano-suspensions as the vitexin oral drug delivery was investigated.1.The micronization of original vitexin drug was researched by the use of anti-solvent recrystallization(DMSO as solvent and water as anti-solvent).The effects of drug concentration,solvent and anti-solvent volume ratio,and stirring speed on the particle size of vitexin were investigated.Furthermore,the parameters of vitexin powder preparation process was optimized by orthogonal experiment:drug concentration of 35 mg/mL,anti-solvent with a solvent volume ratio 1:15,stirring speed 1500 r/min,reaction temperature 4℃.Under this condition,the average particle diameter of vitexin crystal particles was 368.4 nm.The DMSO residue content in the vitexin powder was 1757.10 ppm,which was up to residual organic solvents ICH standards.2.The process of vitexin pwoder into vitexin nano-suspension was prepared by the high pressure homogenization technology.The average particle size of the vitexin nano-suspension with the increase of the homogeneous pressure and cycles of the homogeneous decreased first and then stabilized at last.The stabilizing effect of Poloxamer 188,PEG 300 and egg yolk lecithin on the vetixin nano-crystalline in the system was investigated.The preparation process of vitexin nano-suspension by high pressure homogenization technology was optimized:50 mg vitexin powder was used,added to 50 mL of an aqueous solution of the 5%poloxamer 188.After the pre-dispersed,it was homogenized at 200 and 500 bar respectively for 2 times,and then homogenized at 800 bar for 20 cycles.The stable vitexin nano-suspension was prepared for average particle size of 128.6 nm and Zata potential of 16.78 士 0.89 mV.3.Taking into account that the moldability,reconstitution time,lyophilized time,the average particle diameter as index,the preparation process of vitexin nano-suspension freeze-dried powder was optimized:lyoprotectant 10%mannitol,lyophilized for 48 h.The average particle size of freeze-dried powder obtained was 135.7nm,Zata potential of 17.05 ± 1.40 mV,which was consistent with the one without lyophilizing.It suggested that the stability was not affected by the lyophilizing;the freeze-dried powder reconstitution could restore its original characteristics.Reproducibility and stability experiment illustrated that vitexin nano suspension freeze-dried powder obtained by anti-solvent recrystallization combined with high pressure homogenization had a good reproducibility and stability.4.The content of vitexin was determined by HPLC.This method was sensitive,high precision,reliable,and up to the requirements of the HPLC analysis.The content of vitexin from vitexin nano-suspensions freeze-dried powder was determined as 6.37 ± 0.22%,which was consistent with the theoretical content value of 6.25%.Saturated solubility test showed that the solubility of original vitexin drug and vitexin nano-suspension freeze-dried powder were 30.951 ± 1.03 and 920.583 ±24.76 pm/mL,respectively.The solubility of nano-suspension was higher than original vitexin 28.7 times.The dissolution results of experiments suggested that the accumulated dissolution of± original vitexin drug and the vitexin nano-suspension freeze-dried powder were 33.749 ± 1.88 and 99.44 ±2.95%in 30 min,respectively.The dissolution had also been significantly improved.5.The characters of vitexin nano-suspension freeze-dried powder was analyzed by scanning electron microscopy(SEM),X-ray diffraction(XRD),differential scanning(DSC)and infrared spectroscopy(FTIR).The degree of crystallinity of the vitexin nanosuspension freeze-dried powder was significantly lower than he same component physical mixing.The chemical structure of vitexin nano-suspension freeze-dried powder was not changed.by the isovitexin nano suspension freeze-dried powder were characterized vitexin nanosuspension frozen the degree of crystallinity of the dry powder compared with the component physical mixing significantly reduced,the nanosuspension isovitexin freeze-dried powder in isovitexin chemical structure has not changed.7.The vitexin plasma concentration in rat plasma was determined by HPLC.The method was specific strong impurities and drugs in biological samples got a better separation which did not interfere with the determination.Precision and extraction recovery were higher,the biological samples were stable and up to the quality control requirements for the analysis of biological samples.When the dose of 48 mg/kg,the average plasma concentration was 31.35 μg/mL in 1 min,the average blood concentration was 1.26 μg/mL after 90 min.