The Injection Of Cucurbitacin B In Self-emulsifying Microemulsion Research

Cucurbitacin B is mainly used to treat hepatitis and liver cancer in clinic. In this paper, cucurbitacin B, which is insoluble, was chosen as a lipophlic model drug to prepare microeulsion for intravenous administration, which with expectation of prolonged release and good targeting efficiency of liver to enhance its pharmaceutic effect and reduce adverse effect. Furthermore, the quality of cucurbitacin B microemulsion was evaluated before and after freeze-drying. In addition, a pilot investigation on Pharmacokinetics and tissue distribution, and the results showed the liver targeted objective was acquired.An HPLC method was developed for the assay of cucurbitacin B in drug and preparation. Determination of drug solubility in water and adjuvants showed cucurbitacin B 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. In addition the stability of cucurbitacin B was studied in this paper.Based on the results of the study before formulation, we search for the optimum formulation for the self-microemulsifying drug delivery system of Cucurbitacin B according to the solubility in adjuvants and safety of drugs 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(Ethyl oleate) : m(Cremophor RH) : m(Ethanol) =30: 55: 15, with content 1% of drug. 5% mannitol was used as a protector.The quality of the cucurbitacin B miceoemulsion was evaluated before and after freeze-drying, including partical size and its distribution, configuration, zeta potential, pH, releasing characteristic in vitro and stability. The microemulsion was spheroidal shape through observing by transmission electron microscopy, the mean partical size was 64.7nm and 65.6nm respectively before and after freeze-drying, the zeta potential was approaching zero and negative, the pH value was 6.33 and 6.14 before and after freeze-drying, and releasing characteristic in vitro showed prolonged release characteristic. Results of the stability experiments indicated that the physical and chemical stability of cucurbitacin B microemulsion was much more improved after freeze-dried.An HPLC method was developed for the determination of cucurbitacin B in mouse plasma. Pharmacokinetics of cucurbitacin B aqueous solution and cucurbitacin B microemulsion in mouse after iv administration were investigated. The results showed that cucurbitacin B aqueous solution was accorded with one-compartment model and cucurbitacin B microemulsion was accorded with one-compartment model. Compared with aqueous solution, cucurbitacinB microemulsion was distributed more quickly and eliminated slower, showed some prolonged release characteristic. Their eliminative half-life were 1.536 hour and 2.425 hour, ke were 0.456h^-1 and 0.273h^-1, AUC_0-∞ Were 14.936μg·mL-1·hr and 15.007μg·mL-1·hr separately.An HPLC method was developed for the determination of cucurbitacin B in mouse biological samples. Pharmacokinetics and tissue distribution of cucurbitacin aqueous solution and cucurbitacin B microemulsion in mouse after iv administration were investigated. The results showed that there were more drug distributed in liver, the liver target was obviously enhanced.