Studies On The Docetaxel Submicron Emulsion

The method of high performance liquid chromatography （HPLC） was set up to determine the concentration of docetaxel （DCT）. The total solubility of DCT in different medium and the apparent partition coefficients of DCT were determined. DCT was stable in different conditions（60℃, strong light of 4500Lx±500Lx, 25℃and RH 92.5%）.The method of high-pressure homogenization was applied to prepare DCT intravenous submicron emulsion. The basic formulation of DCT submicron emulsion was determined using single factor investigation; the formulation and the preparation process were optimized by orthogonal design test. Using the stability parameter as the index, the effect of variable components in the formulation such as the amount of oil and oleic acid, the amount and composition of emulsifying agents, pH of the ultimate emulsion, nitrogen protection and the disinfection method; also the effect of variable factors in preparing process such as emulsifying temperature and time of colostrums, the pressure and frequency of the homogenizing process were investigated. The best formulation of DCT intravenous submicron emulsion contained MCT 10%, soybean phospholipids 0.9%, Pluronic F-68 0.6%, DCT 0.2%, oleic acid 0.4%, V_E 0.25%, glycerol 2.25%. The best processing parameters were first emulsifying temperature 70℃, emulsification time 15min, pressure of emulsifying 100Mpa, number of cycle times 6. The DCT intravenous submicron emulsion is a white emulsion with blue lactic light. The mean size was about 170nm and the pH was 5.5～6.5. the viscosity was 0.003pa·s.The physicochemical properties such as particle size, zeta potential, pH value, viscosity and yielding efficiency of DCT intravenous submicron emulsion were studied. The DCT intravenous submicron emulsion showed good compatibility with glucose injection （5%） and sodium chloride injection （0.9%）. The injection was safe to use within 10hr. Simultaneously, accelerated and long-term test were conducted, results showed there was no significant change of the appearance, content of the drug and other parameters.The pharmaceutical safety test results indicated that DCT intravenous submicron emulsion caused no hemolysis. Pharmacokinetics of DCT intravenous submicron emulsion in rats was studied in this paper. A reliable analysis method by HPLC was established to determine the concentration of DCT in rat plasma. After iv administration at a single dosage of 8.0mg·kg^-1 in rats, the concentration-time curve of rats fitted three-compartment model. The results of the drug pharmacokinetics in vivo showed that the DCT intravenous submicron emulsion had a higher AUC, AUMC, MRT compared to DCT injection. The data of experiment were treated by Statistic Quadrature.