Studies On The Docetaxel Emulsion

Objective:Docetaxel is a kind of anticancer drugs taxanes,belongs to the difficult soluble drugs,currently only injectable dosage forms.Through prescription research,the market products are through Tween80,ethanol and other solubilizer to achieve solubilization.The results showed that the solubility of docetaxel was improved by the technique of nanoemulsion,and the freeze-drying process was studied to make it a safe and effective liquid with high stability.Methods:Through prefromulation research and physical and chemical properties survey of docetaxel,provide the basis for subsequent prescription process research and storage conditions.Through the single factor study of the prescription process,central composite design-response surface method optimization,screening the optimal prescription process.The freeze-dried nanoemulsion was prepared by the application of pre-freezing temperature,primary drying,secondary drying process and annealing technology in drying processs.Results:Through the prefromulation study,the method of in vitro analysis of docetaxel was established,which was verified by methodology and met the requirements.The results of strong degradation experiments show that the stability of docetaxel in several conditions is from high to low :light>oxidation>high temperature>strong aci d>strong base.The solubility test of docetaxel showed that docetaxel had a solubilit y of 2.31mg/g in oil containing soybean oil/MCT 1:4.The optimal formulation of docetaxel was as follows:by mass percentage,the composition of the water phase was0.35% poloxamer 188 and the injected water was added to the whole;the oil phase consisted of docetaxel 1%;The temperature of the aqueous and oil phase was 60 ℃;the pH value was about 5.0;the high shear rate was 8.0×103 r/min;high shear time of 10 min,homogeneous pressure of 10000 psi,homogenous 3times.The feasibility of the sterilization process was studied.Finally,the high pressure homogenization technique was combined with the freeze-drying technique.The pre-freezing,primary drying and secondary drying temperature and time were investigated,using 10% sucrose as freeze-dried protective agent,annealing process,preparation of freeze-dried emulsion,and its dilution stability shows good.Conclusions:With emulsion as a carrier,the preparation of docetaxel formulations is feasible,can improve its solubility,and avoid the addition of organic solvents to reduce the irritation of the human body;It is a new direction and development for difficult soluble drugs,but still need to follow up a more comprehensive study.