Study On The Quality And Stability Of Long Circulating Liposome Lyophilized Injection Of Docetaxel

Docetaxel (brand name Taxotere) is the new generation of antineoplastic, which have an excellent curative effect on breast, non-small cell lung, pancreatic, head & neck, ovarian and prostate cancer. At present, the main dosage form of docetaxel coming into the market is the concentrated injecting solution. However, this form is poorly stable and often leads to severe anaphylaxis. Therefore, study of the novel dosage form of docetaxel is of great significance.Firstly, this study has established a quantitative method for the determination of docetaxel drug in the long circulating liposomes. The results showed that the effect of gel column chromatography for separating liposomes and dissociating drugs is better than that of ultra filtration and dialysis method. The validation results also demonstrated that the proposed method is accurate for the determination of encapsulation efficiency of the docetaxel drug.Secondly, the prescriptions of long circulation freeze-drying docetaxol liposomes as well as its cryoprotectants have been investigated. After examination of the effect of the purity of lecithins, drugs, and the proportion of lecithins on the encapsulation efficiency of long circulation liposomes, the optimal prescription was as follows:lecithins concentration 2.5%, the ratio of docetaxel and lecithins 1:25, the ratio of cholesterol and lecithins 1:10, F-127 concentration 1.5%. Based on the appearance of the lyophilized preparation, the particle-size distribution, content, and encapsulation efficiency of the liposome after redissolvation, effective cryoprotectant was screened out. The results showed that the cryoprotectant with the ratio of sucrose sea:algae sugar:lecithin=2:2:1 was of low cost and excellent performance.Finally, the stability and safety of the proposed have also been investigated. The results demonstrated that the product quality is stable for two months under the accelerating environment (40℃; RH=75%). No severe hemolysis and death of animals were observed during the hemolysis test of long circulation docetaxol liposome. The injection LD50 is 198.5±7.0 mg/kg.