Zhang Yi, Cheng Brian Chi-Yan, Zhou Wenjuan, Xu Bing, Gao Xiaoyan, Qiao Yanjiang, Luo Gan
School of Chinese Material Medica, Beijing University of Chinese Medicine, Beijing 100029, China.
College of Professional and Continuing Education, Hong Kong Polytechnic University, Hong Kong 999077, China.
Pharmaceutics. 2019 Oct 9;11(10):519. doi: 10.3390/pharmaceutics11100519.
High shear wet granulation (HSWG) is a shaping process for granulation that has been enhanced for application in the pharmaceutical industry. However, study of HSWG is complex and challenging due to the relatively poor understanding of HSWG, especially for sticky powder-like herbal extracts.
In this study, we used granules to investigate the HSWG process across different scales using quality by design (QbD) approaches.
A Plackett-Burman experimental design was used to screen nine granulation factors in the HSWG process. Moreover, a quadratic polynomial regression model was established based on a Box-Behnken experimental design to optimize the granulation factors. In addition, the scale-up of HSWG was implemented based on a nucleation regime map approach.
According to the Plackett-Burman experimental design, it was found that three granulation factors, including salvia ratio, binder amount, and chopper speed, significantly affected the granule size () of in HSWG. Furthermore, the results of the Box-Behnken experimental design and validation experiment showed that the model successfully captured the quadratic polynomial relationship between granule size and the two granulation factors of salvia ratio and binder amount. At the same experiment points, granules at all scales had similar size distribution, surface morphology, and flow properties.
These results demonstrated that rational design, screening, optimization, and scale-up of HSWG are feasible using QbD approaches. This study provides a better understanding of HSWG process under the paradigm of QbD using granules.
高剪切湿法制粒（HSWG）是一种制粒成型工艺，已在制药行业得到改进应用。然而，由于对HSWG的了解相对较少，尤其是对于粘性粉末状草药提取物，HSWG的研究较为复杂且具有挑战性。
在本研究中，我们使用颗粒通过质量源于设计（QbD）方法研究不同规模下的HSWG过程。
采用Plackett-Burman实验设计筛选HSWG过程中的9个制粒因素。此外，基于Box-Behnken实验设计建立二次多项式回归模型以优化制粒因素。另外，基于成核区域图方法实现HSWG的放大。
根据Plackett-Burman实验设计，发现丹参比例、粘合剂用量和切碎机速度这三个制粒因素对HSWG中颗粒大小（）有显著影响。此外，Box-Behnken实验设计和验证实验结果表明，该模型成功捕捉了颗粒大小与丹参比例和粘合剂用量这两个制粒因素之间的二次多项式关系。在相同实验点，所有规模的颗粒具有相似的粒度分布、表面形态和流动特性。
这些结果表明，使用QbD方法对HSWG进行合理设计、筛选、优化和放大是可行的。本研究在QbD范式下使用颗粒对HSWG过程提供了更好的理解。
