Abstract
Objectives
This study is aimed to explore the blending process of Dahuang soda tablets. These are composed of two active pharmaceutical ingredients (APIs, emodin and emodin methyl ether) and four kinds of excipients (sodium bicarbonate, starch, sucrose, and magnesium stearate). Also, the objective is to develop a more robust model to determine the blending end-point.
Methods
Qualitative and quantitative methods based on near-infrared (NIR) spectroscopy were established to monitor the homogeneity of the powder during the blending process. A calibration set consisting of samples from 15 batches was used to develop two types of calibration models with the partial least squares regression (PLSR) method to explore the influence of density on the model robustness. The principal component analysis-moving block standard deviation (PCA-MBSD) method was used for the end-point determination of the blending with the process spectra.
Results
The model with different densities showed better prediction performance and robustness than the model with fixed powder density. In addition, the blending end-points of APIs and excipients were inconsistent because of the differences in the physical properties and chemical contents among the materials of the design batches. For the complex systems of multi-components, using the PCA-MBSD method to determine the blending end-point of each component is difficult. In these conditions, a quantitative method is a more suitable alternative.
Conclusions
Our results demonstrated that the effect of density plays an important role in improving the performance of the model, and a robust modeling method has been developed.
摘要
目的
探究密度效应对模型性能的影响, 旨在建立一种稳健性更好的模型来实现大黄苏打片混合终点的准确判断
创新点
通过将密度差异变量引入模型校正集中的方法, 建立了一种稳健性更好的原辅料多组分定量校正模型
方法
利用15 批样品建立包含密度效应和未包含密度效应的偏最小二乘回归校正模型, 并利用模型对 3 个未知批次样品进行终点监测。同时, 使用主成分分析-移动块标准偏差算法对3 批样品混合终点进行定性判别。分别使用基于近红外光谱技术的定性、定量分析方法, 实现对大黄苏打片混合终点进行准确监测的目的
结论
粉体密度效应对模型预测性能的提高起到了重要作用。与普通模型相比, 本研究所开发的压力不敏感模型展示了更加稳健的预测性能, 这种稳健建模策略具有一定的推广应用前景.
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Project supported by the National S&T Major Project of China (No. 2018ZX09201011)
Contributors
Si-jun WU performed the experimental research and data analysis, wrote and edited the manuscript. Ping QIU and Pian LI provided samples and other logistics support. Zheng LI provided research funding and participated in research discussion. Wen-long LI participated in research discussion, and wrote and edited of the manuscript. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.
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Si-jun WU, Ping QIU, Pian LI, Zheng LI, and Wen-long LI declare that they have no conflict of interest.
This article does not contain any studies with human or animal subjects performed by any of the authors.
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Wu, Sj., Qiu, P., Li, P. et al. A near-infrared spectroscopy-based end-point determination method for the blending process of Dahuang soda tablets. J. Zhejiang Univ. Sci. B 21, 897–910 (2020). https://doi.org/10.1631/jzus.B2000417
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DOI: https://doi.org/10.1631/jzus.B2000417