盐酸伊立替康脂质体冻干粉针制备及其质量评价.docVIP

盐酸伊立替康脂质体冻干粉针制备及其质量评价 　 作者：邱永宏，戈延茹，王成润，金一 【摘要】 　　目的： 研究盐酸伊立替康脂质体冻干粉针的制备方法，并对其进行初步的质量评价。方法： 以包封率为评价指标，比较四种不同的脂质体制备方法，对硫酸铵梯度法的制备工艺和处方进行单因素考察，筛选出冻干保护剂，并对冻干粉针进行稳定性影响因素试验。结果： 两种主动载药法制得的脂质体包封率更高；硫酸铵梯度法制备过程中，盐酸伊立替康脂质体的包封率受药脂比、硫酸铵浓度、孵育温度、孵育时间影响较大，受胆固醇磷脂比、空白脂质体外水相除盐方法影响较小；采用5％蔗糖与5％乳糖作为冻干保护剂冻干效果更好；所得冻干粉针对温度、光照较为敏感，也易受湿度影响。结论： 采用硫酸铵梯度法，经处方工艺条件的优化，可以获得较高包封率的盐酸伊立替康脂质体，5％蔗糖与5％乳糖是本脂质体较合适的冻干保护剂，初步的稳定性考察结果表明，本脂质体冻干粉针宜低温、避光、密封保存。 【关键词】 盐酸伊立替康； 脂质体； 冻干粉针； 硫酸铵梯度法； 稳定性 　　［Abstract］Objective: To investigate the preparation of irinotecan hydrochloride lyophilized liposomes and to evaluate their quality preliminarily.Methods： Judging by encapsulation efficiency(EE), four different methods for preparing liposomes were compared, the singlefactor test research was applicated to study the formula and the preparation craft, support agents for lyophilization were screened, and the influencing factor test was applicated to study the stability of lyophilized liposomes. Results： High EE of liposomes was achieved by two active loading methods; under the ammonium sulfate gradient method, the EE of irinotecan hydrochloride liposomes was significantly affected by the ratios of drug to lipid, the concentrations of ammonium sulfate, incubation temperature and incubation time, and it was scarcely affected by the ratios of cholesterol to phospholipid or the saltsremoving methods; superior lyophilized powder could be obtained by using 5% sucrose and 5% lactose; the lyophilized powder was sensitive to temperature and illumination, and it was also affected by humidity. Conclusion： With the ammonium sulfate gradient method, after the optimization of the formula and the preparation craft we could get irinotecan hydrochloride liposomes with high EE; 5% sucrose and 5% lactose were suitable support agents for these liposomes. The preliminary assessment of stability showed that the lyophilized liposomes powder should be stored in low temperature, in sealed condition, and away from light. 　　［Key w