Studies On Of Fat Emulsion Injection And Nimodipine Submicron Emulsion For Injection

Fat emulsion injection as a new drug delivery system developed rapidly recently.Its small and uniform particle size distribution,certain stability as well as sufficient supply with essential energy and fatty acid play highly clinical and economic role.The aim of this thesis was to prepare high concentrated fat emulsion injection and nimodipine(NMD)submicron emulsion.The method of high performance liquid chromatography(HPLC)was set up to determine the concentration of soybean oil and lecithin in fat emulsion.Then in vitro analytical method of NMD submicron emulsion was established,which laid the foundation of formulation design.Solubility of NMD in different media was determined,which showed NMD was the most soluble in miglyol 812 compared with the other solvent including soybean oil,oleic acid and water.High pressure homogenization method was used to prepare fat emulsion injection whose formulations were studied using single factor investigation including type and amount of oil phase,emulsifiers,isoosmotic adjusting agent as well as pH value and antioxidant.Factors in procedure profile such as homogenizer,homogenizing cycles and pressure,sterile verification were also presented.Single factor investigation together with orthogonal design was employed to optimize the formulation and procedure of NMD submicron emulsion.The ratio and amount of emulsifiers,oleic acid were take into consideration as three factors to optimize the formulation of NMD emulsion using orthogonal design test in which centrifugation stability constant was take as index.The resultant optimum formulation consisted of soybean oil 2%, miglyol 812 8%,SPC 0.9%,F68 0.3%,NMD 0.02%,oleic acid 0.2%,glycerol 2.25%and V_E0.05%.The same optimum design method was performed to optimize procedure conditions including stirring temperature and time in the pre-emulsion preparation,and homogenizing pressure.The optimum procedure was then obtained,in which,the above three procedure parameters were 70℃,10min and 100MPa,respectively.The mean particle size of NMD emulsion prepared is(153±38)nm and pH value was 7.22.The quality profile of fat emulsion was studied in terms of description,pH value,free fatty acid,peroxide value,anisidine value,lysophospholipid,glycerol,soybean oil and lecithin,all of which met the requirement of fat emulsion injection.Stability test of fat emulsion injection indicated that the preparation produced had no significant change in each index in the stress testing and accelerated testing.The physicochemical properties of NMD submicron emulsion such as microscopic morphology,particle size distribution,ζ-potential,pH value,peroxide value,anisidine value, encapsulation efficiency and temperature of phase change,etc.were investigated.The NMD submicron emulsion showed good compatibility with glucose injection(5%)and physiological saline.The formed liquid mixture was safe to use within 8 hr away from light. The stress testing showed light sensitivity of NMD submicron emulsion with the decrease in NMD content and increase in particle size,peroxide value and anisidine value.While results of accelerated and long-term testing showed there was no significant change in appearance, content of the main drug and other parameters,which implied a good stability of NMD submicron emulsion.