Study On Trichodermin Submicroemulsion For Intravenous Injection

1.Preformulation research of Trichodermin submieroemulsion.A sensitive and preeise HPLC method with high specifieity for Trichodermin determination has been developed.which was not only suitable for Trichodermin content determination.but also suitable for the isolation of Trichodermin and its degradation products or other impurities.Moreover, various external faetors (the alkaline environment, the acid environment, high temperature, light and oxidation) on Trichodermin stability were investigated.2. Formulation design of Trichodermin submicroemulsion and the researeh of preparation techniques.Single factor analysis was employed to evaluate the influence of the concentration of phosphatidyl choline, Poloxamer188and the ratio between oil phase on the relevant properties of the submicroemulsion,respectively.Then based on the results of the single factor analysis, the formulation was optimized by orthogonal design and the stability parameter was taken as the response.In the preparation techniques researeh.the influences of emulsification methods, emulsification temperatures, homogenization pressure on the emulsion quality were investigated respectively and finally the optimal technical parameters were selected.The submicroemulsion prepared with the optimized formulation and preparation technique was stable with uniform particle size distribution and the dimension of90%emulsion droplets was less than150nm.3. The stability study of Trichodermin submicroemulsion.Extreme conditions,such as high temperature,freeze thawing, light and low temperature, were used to investigate the stability of Trichodermin submicroemulsion. The results showed that high temperature and light would lead the drug content..However, the responses of Trichodermin submieroemulsion did not change significantly under low temperature and freezing condition and demix.In addition, the results of physical stability of Trichodermin submicroemulsion in different dilutions showed that the partiele size in them did not inerease significantly with5h.which indicated that the preparation wouldn’t likely cause clot in blood vessel after dilution.4. The pharmacokinetics study of Trichodermin submicroemulsions.A HPLC method was established to determine Trichodermin in vivo.The plasma samples were dealt with liquid-liquid extraction method before determination and norethisterone was selected as the internal standard.This method was simple.quick. sensitive and very suitable for the drug determination in vivo.The pharmacokinetics results of Trichodermin submicroemulsions in rats showed that AUC increased significantly(P<0.05) and the clearance rate(CL)was decreased(P<0.05), which illustrated that the Trichodermin submicroemulsion could maintain a relatively higher concentration in blood and therefore enhancing anticancer effect.