Institute of Pharmacy and Molecular Biotechnology, Department of Pharmaceutical Technology and Biopharmaceutics, University of Heidelberg, Germany.
Eur J Pharm Biopharm. 2011 May;78(1):173-82. doi: 10.1016/j.ejpb.2010.12.015. Epub 2010 Dec 17.
A novel and straightforward multivariate analytical tool for the qualitative determination of powder blend uniformity using on-line Near-Infrared Spectroscopy (NIRS) is presented. The approach combines current chemometric methods, e.g. spectral pre-processing and Principal Component Analysis (PCA), with (1) a new approach of data analysis to determine the end-point of the blending process, (2) building a design space (DS) for blend homogeneity and (3) developing a solid statistical rationale to stop blending according to Quality-by-Design (QbD) principles of FDA's Process Analytical Technology (PAT) initiative. The new approach comprises calculation of Euclidean distances between PCA scores in a multidimensional space and determination of Moving Block Standard Deviations (MBSDs) of successive Principal Component (PC) scores distances to estimate a time-window during blending where spectral variability decreases to a preset minimum. Hotelling's T(2) statistics is then used to monitor and report blend homogeneity. This technique is called "Principal Component Scores Distance Analysis" (PC-SDA). A Central Composite Design resulting in 10 batches mixed in a bin-blender (same composition, different blender fill level, different number of revolutions) was executed. NIR Chemical Imaging (NIR-CI) in combination with Symmetry Parameter Image Analysis (SPIA) was used to verify the NIRS analyzer response and assess homogeneity of all NIR-active components.
提出了一种新颖而直接的多元分析工具，用于使用在线近红外光谱（NIRS）定性确定粉末混合物的均匀性。该方法结合了当前的化学计量学方法，例如光谱预处理和主成分分析（PCA），以及（1）一种新的数据分析方法来确定混合过程的终点，（2）构建混合均匀性的设计空间（DS），以及（3）根据 FDA 的过程分析技术（PAT）倡议的质量源于设计（QbD）原则，开发一种停止混合的可靠统计方法。新方法包括在多维空间中计算 PCA 得分之间的欧几里得距离，并确定连续主成分（PC）得分距离的移动块标准偏差（MBSD），以估计混合过程中光谱变化减小到预设最小值的时间窗口。然后使用 Hotelling 的 T(2)统计量来监测和报告混合均匀性。这种技术称为“主成分得分距离分析”（PC-SDA）。执行了一个中央复合设计，导致 10 批在混合机（相同组成、不同混合机填充水平、不同转数）中混合。近红外化学成像（NIR-CI）与对称参数图像分析（SPIA）结合使用，以验证 NIRS 分析仪的响应并评估所有 NIR 活性成分的均匀性。
