Process optimization by use of design of experiments: Application for liposomalization of FK506
Process optimization by use of design of experiments: Application for liposomalization of FK506
复制标题
DOI：
10.1016/j.ejps.2017.03.007
复制
发表时间：
2017-05
影响因子：
4.6
通讯作者：
Hiroyasu Toyota;T. Asai;N. Oku
中科院分区：
文献类型：
--
作者：
Hiroyasu Toyota;T. Asai;N. Oku
实验设计（DoE）可以利用给药系统加速药物配方的优化，特别是复杂的药物配方。在动物实验中，FK506脂质体（FK506脂质体）是治疗急性脑卒中的有效方法。为了提供FK506脂质体作为脑保护剂，有必要制备具有良好重复性的脂质体。本研究的目的是验证DoE在FK506脂质体工艺优化研究中的有效性。采用Box-Behnken设计评价工艺参数对FK506脂质体性质的影响。多元回归分析结果表明，水化温度与冻融循环对颗粒粒径和包封效率均有交互作用。PBS水化体积的增加导致包封效率的提高。工艺参数对ζ电位无影响。多元回归方程对粒径和包封效率具有较好的可预测性。这些结果表明，制备具有理想性能的脂质体必须考虑生产条件。因此，DoE将是优化脂质体生产条件的有前途的方法。
Design of experiments (DoE) can accelerate the optimization of drug formulations, especially complexed formulas such as those of drugs, using delivery systems. Administration of FK506 encapsulated in liposomes (FK506 liposomes) is an effective approach to treat acute stroke in animal studies. To provide FK506 liposomes as a brain protective agent, it is necessary to manufacture these liposomes with good reproducibility. The objective of this study was to confirm the usefulness of DoE for the process-optimization study of FK506 liposomes. The Box-Behnken design was used to evaluate the effect of the process parameters on the properties of FK506 liposomes. The results of multiple regression analysis showed that there was interaction between the hydration temperature and the freeze-thaw cycle on both the particle size and encapsulation efficiency. An increase in the PBS hydration volume resulted in an increase in encapsulation efficiency. Process parameters had no effect on the ζ-potential. The multiple regression equation showed good predictability of the particle size and the encapsulation efficiency. These results indicated that manufacturing conditions must be taken into consideration to prepare liposomes with desirable properties. DoE would thus be promising approach to optimize the conditions for the manufacturing of liposomes.