| Objective:Flurbiprofen axetil(FA)is a kind of non-steroidal anti-inflammatory drugs,which has analgesic,anti-inflammatory and antipyretic effects.It is widely used in clinic.Its lipid microsphere injection is mainly used for postoperative analgesia and cancer.To establish an in vitro analysis method for FA raw materials and preparations,to study on the formulation and preparation process of FA lipid microsphere injection and to evaluate the quality of FA lipid microspheres injection in vitro,so as to lay a foundation for further research and clinical application of FA.Methods:High performance liquid chromatography(HPLC)was established by consulting literature and Chinese Pharmacopoeia(Chp)2020,which can be used to detect the content of FA bulk drug,the content of preparation and the content of flurbiprofen in the preparation,and carry out methodological validation;To establish an in vitro analytical method for FA raw materials and related substances of preparations.The dosage of oleic acid,the method of adding egg yolk lecithin,the order of oil phase,the temperature of oil phase and water phase,and the order of adding oil phase and water phase were investigated by single factor method;the amount of lecithin,the p H value of colostrum,the amount of soybean oil and the amount of poloxamer 188 were investigated by orthogonal test.The results were analyzed by SPSS 26.The shear rate and high pressure homogenization temperature of colostrum in the preparation process were investigated by single factor method;and the shear time,homogenization pressure and homogenization times of colostrum were investigated by orthogonal test,and the results were analyzed by SPSS 26.The best egg yolk lecithin was determined by determining the properties of FA lipid microsphere injection prepared from nine kinds of egg yolk lecithin.The sterilization temperature was determined by determining the performance of FA lipid microsphere injection.The reproducibility and stability of the determined formula and preparation process were evaluated.Results:The established content and flurbiprofen detection method meet the requirements for the detection of raw materials and formulations of FA lipid microsphere injection.Best prescription:Optimal preparation process:(1)Weigh 8.0% soybean oil,heat it to 65 ℃ in a water bath,weigh 0.4% oleic acid and 1.0% flurbiprofen axetil,and stir it in the above soybean oil to dissolve it into oil phase;(2)Take appropriate amount of water and heat it to 65 ℃,add 2.2% glycerin for injection,188 0.6% Poloxamer,0.068% disodium hydrogen phosphate,1.0% egg yolk lecithin into the above water,put it on a Magnetic stirrer and stir it to dissolve it into water phase;(3)Pour the water phase into the oil phase,wash the inner wall of the beaker containing the water phase with ultra-pure water,and pour it into the oil phase;(4)Shear the mixed solution for 8 min with a high shear disperser 13000 r/min;(5)Adjust the p H value to 9 with 0.1 mol/L sodium hydroxide solution,and obtain colostrum with constant volume of water;(6)Connect the low temperature cooling circulating pump with the high pressure homogenizer to keep the homogenization process at about 10 ℃,and refine the colostrum obtained by 1000 bar circulation for 6 times to obtain the final milk;(7)Filter with 0.65 μm microporous membrane,sub-pack,fill with nitrogen,and seal;(8)Flurbiprofen axetil lipid microsphere injection was obtained after sterilization at121 ℃ for 15 minutes.The optimal egg yolk lecithin is egg yolk lecithin with phosphatidylcholine(PC)content of 70%~80%.The compatibility stability,acceleration stability and long-term stability are good.Conclusion:This subject has completed the screening and optimization of the formula and preparation process of FA lipid microsphere injection,initially established the quality standard of FA lipid microsphere injection,and carried out the stability study,laying a foundation for the in-depth research and clinical application of FA lipid microsphere injection. |
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