Sparén Anders, Hartman Madeleine, Fransson Magnus, Johansson Jonas, Svensson Olof
Appl Spectrosc. 2015 May;69(5):580-9. doi: 10.1366/14-07645. Epub 2015 Apr 1.
Raman spectroscopy can be an alternative to near-infrared spectroscopy (NIR) for nondestructive quantitative analysis of solid pharmaceutical formulations. Compared with NIR spectra, Raman spectra have much better selectivity, but subsampling was always an issue for quantitative assessment. Raman spectroscopy in transmission mode has reduced this issue, since a large volume of the sample is measured in transmission mode. The sample matrix, such as particle size of the drug substance in a tablet, may affect the Raman signal. In this work, matrix effects in transmission NIR and Raman spectroscopy were systematically investigated for a solid pharmaceutical formulation. Tablets were manufactured according to an experimental design, varying the factors particle size of the drug substance (DS), particle size of the filler, compression force, and content of drug substance. All factors were varied at two levels plus a center point, except the drug substance content, which was varied at five levels. Six tablets from each experimental point were measured with transmission NIR and Raman spectroscopy, and their concentration of DS was determined for a third of those tablets. Principal component analysis of NIR and Raman spectra showed that the drug substance content and particle size, the particle size of the filler, and the compression force affected both NIR and Raman spectra. For quantitative assessment, orthogonal partial least squares regression was applied. All factors varied in the experimental design influenced the prediction of the DS content to some extent, both for NIR and Raman spectroscopy, the particle size of the filler having the largest effect. When all matrix variations were included in the multivariate calibrations, however, good predictions of all types of tablets were obtained, both for NIR and Raman spectroscopy. The prediction error using transmission Raman spectroscopy was about 30% lower than that obtained with transmission NIR spectroscopy.
拉曼光谱可作为近红外光谱（NIR）的替代方法，用于固体药物制剂的无损定量分析。与近红外光谱相比，拉曼光谱具有更好的选择性，但对于定量评估而言，子采样一直是个问题。透射模式下的拉曼光谱减少了这一问题，因为在透射模式下可测量大量样品。样品基质，如片剂中药物物质的粒径，可能会影响拉曼信号。在本研究中，系统地研究了固体药物制剂在透射近红外和拉曼光谱中的基质效应。根据实验设计制备片剂，改变药物物质（DS）的粒径、填充剂的粒径、压缩力和药物物质含量等因素。除药物物质含量在五个水平变化外，所有因素均在两个水平加一个中心点变化。对每个实验点的六片片剂进行透射近红外和拉曼光谱测量，并对其中三分之一的片剂测定其DS浓度。近红外和拉曼光谱的主成分分析表明，药物物质含量和粒径、填充剂的粒径以及压缩力均会影响近红外和拉曼光谱。为进行定量评估，应用了正交偏最小二乘回归。实验设计中变化的所有因素在一定程度上均影响DS含量的预测，对于近红外和拉曼光谱而言，填充剂的粒径影响最大。然而，当在多变量校准中纳入所有基质变化时，近红外和拉曼光谱均能对所有类型的片剂进行良好预测。使用透射拉曼光谱的预测误差比透射近红外光谱低约30%。
