| Brucea javanica oil is the extracts of Brucea javanica mature fruit, it has a broad anti-tumor activity. Brucea javanica oil can inhibit the proliferation of a variety of cancer cells and its toxicity is low. Microemulsion as a potential carrier for injectable drug with good application perspcetives,can improve the solubility of drugs,lengthen the drug`s acting time in vivo due to its slow release from microemulsion,and reduce pain caused by injection due to its low viscosity.In this study, We seleeted microemulsion as drug carrier and Brucea javanica oil as the model drug to prepare Brucea javanica oil microemulsion.We investigated the charaeters of Brucea javanica oil correlated. Then by the pseudo-temary phase diagrams,we investigated the formulation and formula technology of microemulsion, obtained the formula of microemulsion with low content of surfaetants,good solubilization and stable quality,and prepared Brucea javanica oil microemulsion.The quality of Brucea javanica oil microemulsion was assessed by laser nano-sizer analyzer,GC and so on.This work aimed to supply valuable trials for the preparation of injectable microemulsion for Chinese medieinal ingredients with poor solubility.We chose the soybean phospholipids, Cremophor EL,Cremophor RH,tween-80, span-80,poloxamer F68, Solutol HS15 as surfactants.ethanol,iso-propyl alcohol, n-butanol,sorbitol,Polyethylene glycol 200, Polyethylene glycol 400 and glycerine as co-surfactants.isopropyl myristate,MCT and injectable soybean oil as oil phase.On the basis of the Pseud-triangular phase diagrams obtained from titration method,the effects on the area of microemulsion and the solubilization amounts of oil of various elements(surfactants,co-surfactants and oils)were investigated to search rational microemulsion formula. We found that the area of microemulsion and the solubilization amounts of oil was small with various surfactants single used.The system composed of Solutol HS15/ sorbitol / isopropyl myristate / water showed the best effect.After further research we found that the area of microemulsion and the solubilization amounts of oil was better than other microemulsion formula.Using the Solutol HS15 as surfactants,the effeets of Km(the mass ratio of surfaetant / co-surfaetant) and the mass ratio of surfaetant/oil on the area of microemulsion were further investigated.Finally we aseertained the Brucea javanica oil mieroemulsion formula,the optimized one was the system of Solutol HS15/ sorbitol / isopropyl myristate/ Brucea javanica oil(27:9:9:5).The Brucea javanica oil mieroemulsion prepared,The quality of Brucea javanica oil microemulsion was assessed. Brucea javanica oil microemulsion was uniform and transparent fluid with light blue,its viscosity was 5.5mm3·s-1,with the conductivity 23.7μs·cm-1. The particle diameter and its distribution of Brucea javanica oil microemusion were determined by Nano-ZS 90 grainsize analyzer,its mean diameter was 23.8 nm.We established an accurate method for the determination of oleic acid of Brucea javanica oil in the microemulsion. oleic acid of Brucea javanica oil was determined by GC,the line rang was 0.115～0.575mg/mL,(R2=0.9996,n=5).Its average recovery rate was 100.01% and the RSD 0.39%.The method was convenient, rapid,accurate and suitable for assay of oleic acid of Brucea javanica oil in the microemulsion,and the mean content of oleic acid in Brucea javanica oil microemulsion was 84.02mg/mL.Using the classical constant temperature method, taken appearance, size and distribution, content as indicators, the preliminary evaluation of the stability of the microemulsion system has been done. The sample bene placed under 40,50,60,70℃for eight days, The reaction rate constant at every temerature bene calculated.The reaction rate constant at 25℃been calculated by linear regression. Finally, a validity period about 568 days been obtained. The experimental results showed that the Brucea javanica oil microemulsion is basic stable.Then,pharmacodynamics and side effects of Brucea javanica oil microemulsion have been studied. Hela cells was cultured in vitro, Different concentrations of Brucea javanica oil microemulsion and emulsion been given, affecting different time, Using MTT method the rate of the tumor suppressor was assayed and tumor suppressor mapping curve was drawn.The cell morphology was observed under the optical microscope to study the change of Hela cells` morphology before and after Brucea javanica oil microemulsion and general emulsion. The results show that the Brucea javanica oil microemulsion better than its emulsion in the tumor suppressor effect. As the drug concentration and affacting time increased, the rate of tumor suppressor increased. Hela cells treated with Brucea javanica oil microemulsion, cell morphogenesis changed significantly, with the extension of time, cell appear apoptosis, cell debris can be seen under the microscope. Using New Zealand white rabbits for study of Brucea javanica oil microemulsion vascular irritation, and compared with the Brucea javanica oil emulsion, results showed that the blood vessels irritatant of Brucea javanica oil Brucea javanica oil microemulsion smaller than its emulsion. Allergic test and in vitro hemolytic experiments indicate that Brucea javanica oil microemulsion`s more safe than its emulsion.In conclusion, The brucea javanica oil microemulsion were obtained through this study with low contents of emulsifier and good stability,which significantly improved the solubility of brucea javanica oil . Its tumor suppressor effects is significant,its side-effects is small. This study supply valuable trials for the preparation of injectable microemulsion for Chinese medicinal ingredients with poor solubility.
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