| Traditional Chinese medicine luteolin is a natural flavonoid compound,mostly in the form of glycosides,which can be isolated from a variety of natural herbs and vegetables and fruits.The main pharmacological effects of luteolin include anti-inflammatory,antibacterial,anti-fibrosis,anti-oxidation,anti-tumor,etc.Multiple biological activities make it one of the most popular traditional Chinese medicines among researchers in recent years.Due to the biggest disadvantage of luteolin-poor water solubility,the clinical application and development of luteolin has been greatly hindered.Therefore,improving the water solubility of luteolin is the most important measure to solve the limitation of clinical medicine.In order to improve the solubility of luteolin and increase the drug loading,we used the biocompatible vitamin E polyethylene glycol succinate(TPGS)as the stabilizer and luteolin as the model drug to prepare luteolin nano suspension.In this experiment,nano suspensions were prepared by micro precipitation high pressure homogenization method with a certain homogenization pressure and homogenization times,and the types of stabilizers and the proportion of stabilizers and drugs were screened by single factor screening method.Taking particle size,stability,polymer dispersion index(PDI)and zeta potential as reference indexes,the best stabilizer and the ratio of stabilizer to drug were selected,and the preparation prescription was optimized.Finally,the ratio of stabilizer to drug was determined as 1:1.The preparation of nano suspension was investigated: the particle size of nano suspension measured by Malvern laser particle sizer was about 210 nm,the potential was about(-16.3±0.78)m V,the dispersibility and storage stability were good.Transmission electron microscopy(TEM)images show that the nanosuspension is uniformly dispersed spherical or elliptical nanoparticles,and the results of differential scanning calorimetry(DSC)and X-ray powder diffraction(XRD)show that the drug exists in crystalline form,and the particle size of luteolin nano suspension has only changed,but its crystal form has not changed significantly.The best wavelength of luteolin was 350 nm,which was obtained by scanning with UV spectrophotometer.Under this wavelength,the standard curve was established to determine luteolin content in luteolin nano suspension.The results showed that luteolin content in the preparation reached about 60%.The results of supersaturated dissolution in vitro showed that at p H 1.2 and p H 6.8,the supersaturated dissolution of luteolin drug substance was always lower than the corresponding equilibrium solubility,and the supersaturated dissolution of luteolin nano suspension was always higher than the corresponding equilibrium solubility,indicating that the supersaturation of the preparation was high;After the p H of the dissolution medium was adjusted to 6.8,although the dissolution level decreased significantly,the supersaturated dissolution of luteolin nanosuspension was always higher than the corresponding equilibrium solubility,and the supersaturated dissolution level gradually stabilized after 150 min,indicating Nanosuspension can maintain a high level of supersaturated dissolution.Compared with the raw LUT,the prepared nano suspension not only improved the solubility of luteolin,but also significantly improved the dissolution performance of the drug.To establish an HPLC determination method for the drug content of luteolin oral nanosuspension,the absorption of drugs in different parts of duodenum,jejunum,ileum and colon was studied by the model experiment of eversion intestine in rats.Results: The absorption of drugs in the intestine of rats was mainly concentrated in the duodenum and jejunum,indicating that the best sites for drug absorption were the duodenum and jejunum;The drug absorption of the nano-suspension group is greater than that of the control group,indicating that the nano-suspension can improve the absorption of the drug in the intestine,which will help to improve the bioavailability of the drug in vivo. |
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