Pestieau Aude, Krier Fabrice, Thoorens Grégory, Dupont Anaïs, Chavez Pierre-François, Ziemons Eric, Hubert Philippe, Evrard Brigitte
Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
Laboratory of Pharmaceutical Technology, Department of Pharmacy, C.I.R.M., University of Liège, 4000 Liège, Belgium.
J Pharm Biomed Anal. 2014 Sep;98:60-7. doi: 10.1016/j.jpba.2014.05.002. Epub 2014 May 10.
The aim of this study was to use the near-infrared spectroscopy (NIRS) as a process analytical tool to evaluate the conformity of paracetamol tablets in terms of four Pharmacopoeia tests (content uniformity, hardness, disintegration time, friability) and to control in-line blend uniformity. Tablets were manufactured by direct compression. Three different active pharmaceutical ingredient (API) concentrations were manufactured and three different compaction pressures were used. Intact tablets were analysed by transmission mode with NIRS prior to European Pharmacopoeia tests that were used as reference methods. Partial least square (PLS) regression was selected to build the prediction NIR models for content uniformity, tablet hardness and disintegration time. The prediction of NIR content uniformity and tablet hardness methods were validated using the accuracy profile approach. The values of the root mean squared error of calibration (RMSEC) and the root mean squared error of prediction (RMSEP) for the disintegration time indicated the robustness and the global accuracy of the NIR model. Regarding the tablet friability test, the classification was based on K-nearest neighbours (KNN). Then tablet NIR analyses successfully allowed the prediction of their conformity. Compared to the time consuming Pharmacopoeia reference methods, the benefit of this nondestructive method is significant, especially for reducing batch release time.
本研究的目的是使用近红外光谱（NIRS）作为一种过程分析工具，根据四项药典测试（含量均匀度、硬度、崩解时间、脆碎度）评估对乙酰氨基酚片的一致性，并控制在线混合均匀度。片剂采用直接压片法制造。制备了三种不同的活性药物成分（API）浓度，并使用了三种不同的压片压力。在用作参考方法的欧洲药典测试之前，采用透射模式通过NIRS对完整片剂进行分析。选择偏最小二乘（PLS）回归来建立含量均匀度、片剂硬度和崩解时间的近红外预测模型。采用准确度曲线法验证了近红外含量均匀度和片剂硬度方法的预测结果。崩解时间的校准均方根误差（RMSEC）和预测均方根误差（RMSEP）值表明了近红外模型的稳健性和整体准确性。对于片剂脆碎度测试，分类基于K近邻算法（KNN）。然后，片剂的近红外分析成功地实现了对其一致性的预测。与耗时的药典参考方法相比，这种无损方法的优势显著，特别是在缩短批放行时间方面。
