Abstract

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.

Comprehensive study of solid pharmaceutical tablets in visible, near infrared (NIR), and longwave infrared (LWIR) spectral regions using a rapid simultaneous ultraviolet/visible/NIR (UVN) + LWIR laser-induced breakdown spectroscopy linear arrays detection system and a fast acousto-optic tunable filter NIR spectrometer

Clayton S.C Yang, Feng Jin, Siva R. Swaminathan, Sita Patel, Evan D. Ramer, Sudhir B. Trivedi, Ei E. Brown, Uwe Hommerich, and Alan C. Samuels
Opt. Express 25(22) 26885-26897 (2017)

Broadband photon time-of-flight spectroscopy of pharmaceuticals and highly scattering plastics in the VIS and close NIR spectral ranges

Dmitry Khoptyar, Arman Ahamed Subash, Sören Johansson, Muhammad Saleem, Anders Sparén, Jonas Johansson, and Stefan Andersson-Engels
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Optical system for tablet variety discrimination using visible/near-infrared spectroscopy

Yongni Shao, Yong He, and Xingyue Hu
Appl. Opt. 46(34) 8379-8384 (2007)

Density-dependent determination of scattering properties of pharmaceutical tablets using coherent backscattering spectroscopy

Annika Häffner, Philipp Krauter, and Alwin Kienle
Opt. Express 26(16) 19964-19971 (2018)

Spatial mapping of proteoglycan content in articular cartilage using near-infrared (NIR) spectroscopy

Isaac O. Afara, Hayley Moody, Sanjleena Singh, Indira Prasadam, and Adekunle Oloyede
Biomed. Opt. Express 6(1) 144-154 (2015)