葫芦素B脂肪乳注射液处方及制备工艺的研究

Formulation and preparation of cucurbitacin B lipid emulsion

目的确定葫芦素B脂肪乳注射液的最优处方和最佳制备工艺。方法利用高压均质技术制备葫芦素B脂肪乳注射液,分别对药物和磷脂的加入方式、均质压力和次数、pH值和灭菌方式等制备工艺进行了考察,对油相组成、磷脂、F68和油酸钠的用量及抗氧剂的选择进行了优化。结果确定了最终的处方和制备工艺:将葫芦素B与2.0%磷脂溶解于无水乙醇中,70℃氮气流下挥干无水乙醇后加入2.5%长链三酰甘油、7.5%中链三酰甘油及0.05%dl-α-生育酚,70℃继续搅拌使其溶解,2.5%注射用甘油、0.2%F68和0.3%油酸钠分散于适量注射用水中,70℃加热搅拌至溶解;油相加入水相至15 000 r.min-1高速搅拌5 min得初乳;将初乳pH值调至8.0,定容,40℃下,700 bar高压均质8次;灭菌条件为121℃热压蒸汽灭菌8 min。结论所制备葫芦素B脂肪乳注射液具有较好的物理化学稳定性。

Objective To optimize the formulation and preparation of cucurbitacin B lipid emulsion.Methods High pressure homogenization was used to prepare cucurbitacin B lipid emulsion.The factors influencing the stability of the lipid emulsion,such as the drug loading methods,homogenization conditions,pH,sterilization methods,oil phase composition,phospholipids,F68,sodium oleate and antioxidants were investigated.Results The final formulation and preparation were as follows： Cucurbitacin B and 2.0% lecithin were dissolved in dehydrated alcohol.After dissolving uniformly,the dehy-drated alcohol was evaporated with stream nitrogen at 70 ℃.Then,the mixture was dispersed in oil composed of LCT（2.5%）,MCT（7.5%） and dl-α-tocopherol（0.05%）.F68（0.2%） and glycerol（2.5%） were heated to 70 ℃ and agitated until uniformly dissolved.Finally,the oil phase was added slowly to the water phase with high speed shear mixing at 15 000 r.min-1 for 5 min to obtain coarse emulsion.The pH was adjusted to 8.0 and the volume made up by purified water.After that,the coarse emulsion was subjected to high-pressure homogenization at 700 bar for 8 cycles to get the final emulsion at 40 ℃.Then the emulsion was sterilized by autoclaving for 8 min at 121℃.Conclusion Cucurbitacin B lipid emulsion prepared in this study is stable.