Department of Chinese Medicine Informatics, Beijing University of Chinese Medicine, Beijing, People's Republic of China.
Beijing Key Laboratory of Chinese Medicine Manufacturing Process Control and Quality Evaluation, Beijing, People's Republic of China.
Drug Des Devel Ther. 2021 Mar 30;15:1425-1440. doi: 10.2147/DDDT.S295825. eCollection 2021.
Understanding raw material variability and its impact on product quality are crucial for developing robust pharmaceutical processes. This work aimed to study the effects of spray drying conditions on properties of the spray dried saponin (PNS) powders as well as the subsequent intra-batch dissolution variability of PNS hydrophilic matrix tablets.
The Plackett-Burman design was applied to screen the critical process parameters (CPPs). Then, the Box-Behnken design was used to investigate the relationship between the CPPs and the physiochemical properties of spray dried PNS powders. The PNS hydrophilic matrix tablets containing 57% spray dried PNS powders were directly compressed. The partial least squares (PLS) regression was used to uncover the hidden multivariate relationships among the CPPs, intermediate powder properties, and tablet quality attributes.
The identified CPPs were the feed concentration, the inlet air temperature, and the atomization pressure. It was found that the CPPs exerted little impact on chemical properties of spray dried PNS powders, but had significant impact on physical properties, such as particle size, specific surface area, bulk density, hygroscopicity, and inter-particle porosity, etc. Latent variable modeling results revealed that the high inlet air temperature of spray drying process could produce PNS powders with low moisture content and high hygroscopicity, which were beneficial to reduce the intra-batch dissolution variability of PNS hydrophilic matrix tablets. Finally, a design space of the spray drying process was built in order to ensure the dissolution consistency.
Our research provided a reference for improving the spray drying conditions in order to ensure the dissolution consistency of the PNS hydrophilic matrix tablet.
了解原料药的变异性及其对产品质量的影响对于开发稳健的制药工艺至关重要。本工作旨在研究喷雾干燥条件对喷雾干燥皂素（PNS）粉末性质的影响，以及 PNS 亲水性基质片随后的批内溶出变异性。
采用 Plackett-Burman 设计筛选关键工艺参数（CPPs）。然后，采用 Box-Behnken 设计研究 CPPs 与喷雾干燥 PNS 粉末物理化学性质之间的关系。含有 57%喷雾干燥 PNS 粉末的 PNS 亲水性基质片直接压片。采用偏最小二乘（PLS）回归法揭示 CPPs、中间粉末性质和片剂质量属性之间隐藏的多变量关系。
确定的 CPPs 为进料浓度、进风温度和雾化压力。发现 CPPs 对喷雾干燥 PNS 粉末的化学性质影响不大，但对物理性质如粒径、比表面积、堆密度、吸湿性和颗粒间孔隙率等有显著影响。潜在变量建模结果表明，喷雾干燥过程中的高进风温度可产生低含水量和高吸湿性的 PNS 粉末，有利于降低 PNS 亲水性基质片的批内溶出变异性。最后，为确保溶出一致性，构建了喷雾干燥工艺的设计空间。
本研究为改善喷雾干燥条件以确保 PNS 亲水性基质片的溶出一致性提供了参考。
