Preparation And Characterizations Of 10% Fat Emulsions For Injection

Parenteral nutrition fat emulsion is one of the source to supply energy for the body. Besides energy supplyment, it also can provide essential fatty acids. It was introducted about 40 years ago,during the last 50 years, the fat emulsion has developed from long-chain triacylglycerol (LCT) to SMOF, there are already many products in use in china. The fat emulsion is very safe,and without stimulation to vein.It not only supplied high-energy for patients rapidly, but also had good compatibility with amino acids, vitamins, electrolytes and other therapeutic transfusion.It has become an important research agents to improve drug efficacy.According to the classical prescription, which has been unveiled, only through optimizing the technological aspects, it can not get stable fat emulsion. On the basis of the public prescription,this subject aims to investigate fat emulsion through the optimization of prescription and process indicators,in order to meet the standards of it. Meanwhile this investigation provided essential experimental parameters for the study of series of fat emulsions preparation and the preparation of drug-loaded fat emulsions.Through the pre-experiment, the study preliminarily ensured the important factors and levels, and the prescriptions were adjusted by adding a stabilizing agent—oleic acid. In order to avoid the side effect, a single index cased in the microscopic fields, the subject established multi-index detection methods. Based on the pre-experiment, the investigation of the primary emulsion involved mixed order, pHase proportion,oleic acid dosage, mixed temperature, stirring speed and stirring time. TaKe the floating-oil level and merger rate of emulsion drops as index,the formulation and procedure of fat emulsions were optimized by Uniform Design, and finally qualified fat intravenous emulsion was investigated. The optimal prescription for fat emulsion were as follows:injected oil 10%; soybean pHospHolipidsl.2%; glycerol 2.5%; oleic acid0.2%; injection water increased to 100%. The optimal procedures of primary emulsion were as follows:the soybean pHospHolipids and oleic acid was added in soybean oil, afterwards stired for 5min with high-speed at 10000r/min as the oil pHase,when the solution system was fully dispersed;the glycerol was added in WFI as the water pHase; the mixed temperature was set at 60℃,70% of the aqueous pHase was transferred into the digital mixer, the stirring speed was set at 6000r/min when the oil pHase was slowly added into the digital mixer. When all of the oil pHase was added, set the stirring speed at 11000r/min and stired for 13min, afterwards adding the remaining water, use 10% NaOH to adjust PH to 8.0,finally in order to eliminate air bubbles,the solution was stired at 3000r/min for 2min, so is the primary emusion.The investigation of high pressure procedures mainly included:single stage homogeneous and two stage homogeneous of high-pressure homogenization machine, high pressure,middle pressure and emulsified times of high pressure. The middle pressure before high pressure can significantly minify the particle size distribution of caused by single high-pressure.The subject studied the interaction between pressure and emulsified times by Uniform Design. The optimal procedures of high-pressure homogenization were as follows:Under the situation of zero pressure, in order to eliminate the residual air bubbles and maKe the experiments carried out smoothly, let the primary emulsions cycle one or twice times in the Homogeneous machine.1st stage pressure was set at 100bar,2nd stage pressure was set at 600bar, cycled three times, then 2nd stage pressure was adjusted to 1000bar, cycle four times, then the effluent solution was unsterilized fat emulsion.After packaged, the products was put into autoclave to be sterilized for 15min, and the time upto 121℃was controlled at 14min, that is the final product.The investigation about characterizations of 10% fat emulsion included:stability after sterilization, high-temperature accelerated stability, long-term stability, PH value and ZETA potentials. Fat emulsion has good stability after accelerated and long-term experiments, measurement,the PH value was between 6-7, and the Zeta potentials were very big. Hemolytic, Systemic and allergic were two important indicators for injection, investigation about the two indicators showed that there were no hemolytic and systemic allergic. The result showed that the fat emulsions was stable,and consistented with the injection safety requirements for clinical use.