Study On Docetaxel Self-microemulsion For Intravenous Injection

Docetaxel is a novel anticancer drugs. It is effective for ovarian cancer,breast cancer,non-small cell lung cancer,esophageal cancer,head and neck cancer and other tumor diseases.At present, the commercial product of docetaxel still adopted Tween 80 and ethanol as injection solvents, Tween 80 was used as solubilizer and ethanol as auxiliary solvent, which was packed separated as condensed injection solution and solvent in two packages. Although the prescription use a relatively less toxic solubilizer Tween 80 and ethanol as solvents, but still exsit complicated operation in clinical use and Tween 80 is easy cause allergies and hemolytic effects.In order to eliminate the existed a series of problems which docetaxel produced in clinical use and solve the lower solubility of docetaxel, a docetaxel self-microemulsion for intravenous injection was developed in this study, so as to provide fundmental work for new dosage form research of docetaxel. The main contents of the research are follows.1. Preformulation research of docetaxel self-microemulsion.An HPLC method was developed for the assay determination of docetaxel self-emulsifying system on the preformulation study, this method is sensitive,precise,convenient specific to self-emulsifying system for the determination of the drug.The solubility of docetaxel in various oils phase and surfactant and cosurfactant was measured, also observed the effect through a variety of oil phase and surfactant of the compatibility, choose with strong emulsifier and higher solubility for drug an, as the self-emulsifying drug delivery system of basic prescription screening. Determinnation of drug solubility in water and adjuvants showed DOC was insoluble in water and relatively more soluble in various oil,emulsifier and co-emulsifier.The oil-water participate coefficient showed relatively strong lipophlic property of drug.2. The preparation of docetaxe self-emulsifying system.Based on the results of the study before formulation, we search for the optimum formulation for the self-microemulsifying drug delivery system of DOC, the drawing of pseudo-ternary phase diagram of blank self-microemulsifying drug delivery system and analysis partical size. The constitution of optimum formulation is as follows:m(MCT): m(Soultol HS15):m(PEG 400)= 3:8:4, with content 2% of drug.3. Docetaxel self-emulsifying system and the stability of the physical and chemical properties.According to the appearance of SEDDS, before and after emulsiyfing, the emulsified time, the droplet size after self-emulsification, content and stability test of DOC, the quality of SEDDS of DOC was evaluated.Meanwhile, we also studied the shifts of the self-emulsifying efficiency by changing temperature, dispersed media and dispersed methods and the effect of the different dispersed mdedium, dilution on the droplet size.4. The pharmacodynamic study of docetaxel self-microemulsion in rats.An HPLC method was developed for the determination of docetaxel in mouse plasma. Pharmacokinetics of docetaxel injection and docetaxel self-microemulsion in mouse after iv administration were investigated.The plasma samples were dealt with methanol before determination.The method was simple,quick,sensive and very suitable for the drug determination in vivo. The pharmmacokinetics results of docetaxel self-microemulsions showed that docetaxel injection and docetaxel self-microemulsion was accored with double-room double.