Optimization Of Prescription And Preparation Of Propofol Emulsion Injection And Quality Evalution

Propofol is a clinical intravenous anesthetic medicine,It is widely used in clinic because of its fast action,easy control and so on,In this study,propofol was used to study the effects of propofol on emuision injection.The HPLC analysis method with high sensitivity and good specificity determination of propofol content and related substances was established,The conditions of chromatography were eighteen alkyl silane bonded silica gel column,and the column temperature was about 30 degrees.275 and 254nm were used as the detection wavelength.The mobile phase A was 0.2%sodium dihydrogen phosphate aqueous solution,pH value to 3,mobile phase B:acetonitrile by gradient elution program,the flow rate is 1 ml/min.Under the above conditions,the A and B can be separated from the main peak.The degree of separation between adjacent peaks is not less than 1.5.At the same time,a high performance liquid chromatography(HPLC)method was developed for the determination of phosphatidyl choline.Through prescription screening,with the injection of soybean oil and medium chain triglycerides 1:1 ratio of mixed oil as oil phase carrier,The 1.2%of phospholipid and 0.05%of oleic acid was screened to ensure the stability of the emulsion.and through the orthogonal experimental design,select the appropriate preparation process parameters of high shear emulsification,with low pressure homogeneous preparation,high pressure homogenization method at 300bar to prepare propofol emulsion injection.And the electron beam and particle size distribution were used to characterize.And on the basis of laboratory prescription and preparation process to optimize the further process,Preparation of colostrum by using 100bar pressure homogenization instead of laboratory Obar homogenization,The filtration pressure is less than 40Kpa,or to reduce the insoluble particles of 1 um;When the filling nitrogen pressure is 30Kpa,the residual oxygen content is3.010.4%;Sterilization condition is 121℃,12min,when the industrial steam pressure is larger than 0.3Mpa,cooling water pressure is 0.2Mpa,The F0 value is more than 12 under the conditions of heating and cooling can shorten the time and can maintain a low rate of damage,On the basis of the optimization of the pilot production process,The average particle size is 245.2±10nm.The influence factors test,accelerated test and long-term test were carried out on the propofol emuision injection,The concentrations of pH,osmotic pressure,the content of propofol,the related substances,the size distribution of the particles and the phosphatidylcholine were measured,The results showed that the emuision Injection produced by the pilot process was stable under the conditions of strong light,high temperature,low temperature cycle,6 months accelerated test and long-term test for 24 months.