Bodson C, Rozet E, Ziemons E, Evrard B, Hubert Ph, Delattre L
Laboratory of Pharmaceutical Technology, University of Liege, 1 Avenue de l'Hôpital, 4000 Liège, Belgium.
J Pharm Biomed Anal. 2007 Oct 18;45(2):356-61. doi: 10.1016/j.jpba.2007.05.015. Epub 2007 May 21.
The goal of this study was to apply the Process Analytical Technology FDA's initiative in pharmaceutical tablets manufacturing. Near Infrared Spectrophotometry (NIRS) was used as a non-destructive, very fast technique requiring no sample preparation. Direct compression powder blends containing Diltiazem HCl as a model drug were pressed into tablets for the calibration and the validation steps. First, a partial least squares model was built to calibrate the NIR spectrometer. Then, this model was validated and compared with a validated UV spectrophotometry reference method. For this comparison, the Bland and Altman's statistical method was applied. The manufacturing process was validated by producing three batches at three different concentration levels. The NIR analysis of these batches was performed during 3 days. This study shows that NIRS can be used to validate the whole manufacturing process and not only as an analytical method for tablets assay. NIRS is an interesting tool to show possible variations during the manufacturing process which could lead the finished product to fall outside of specifications.
本研究的目的是将过程分析技术应用于美国食品药品监督管理局在制药片剂生产方面的倡议。近红外分光光度法（NIRS）被用作一种无损、快速且无需样品制备的技术。将含有盐酸地尔硫䓬作为模型药物的直接压片粉末混合物压制成片剂，用于校准和验证步骤。首先，建立偏最小二乘模型来校准近红外光谱仪。然后，对该模型进行验证，并与经过验证的紫外分光光度法参考方法进行比较。为此比较应用了布兰德和奥特曼的统计方法。通过在三个不同浓度水平生产三批产品来验证制造过程。在三天内对这些批次进行近红外分析。本研究表明，近红外光谱法可用于验证整个制造过程，而不仅仅作为片剂含量测定的分析方法。近红外光谱法是一种有趣的工具，可显示制造过程中可能导致成品超出规格的变化。
