Matrix Effects in Quantitative Assessment of Pharmaceutical Tablets Using Transmission Raman and Near-Infrared (NIR) Spectroscopy

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.

[1]  R. Szostak,et al.  Quantitative determination of diclofenac sodium and aminophylline in injection solutions by FT-Raman spectroscopy. , 2006, Journal of pharmaceutical and biomedical analysis.

[2]  R. Szostak,et al.  FT-Raman quantitative determination of ambroxol in tablets , 2004 .

[3]  Rotating samples in FT-RAMAN spectrometers. , 1997, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[4]  J. Sjöblom,et al.  Quantitative FT-Raman analysis of two crystal forms of a pharmaceutical compound. , 1997, Journal of pharmaceutical and biomedical analysis.

[5]  R. Yu,et al.  Quantitative analysis of powder mixtures by Raman spectrometry: the influence of particle size and its correction. , 2012, Analytical chemistry.

[6]  R. Szostak,et al.  Quantitative determination of acetylsalicylic acid and acetaminophen in tablets by FT-Raman spectroscopy. , 2002, The Analyst.

[7]  Y. Roggo,et al.  A review of near infrared spectroscopy and chemometrics in pharmaceutical technologies. , 2007, Journal of pharmaceutical and biomedical analysis.

[8]  J. Coello,et al.  Near-infrared spectroscopy in the pharmaceutical industry. , 1998, The Analyst.

[9]  Roman Szostak,et al.  Quantitative determination of captopril and prednisolone in tablets by FT-Raman spectroscopy. , 2006, Journal of pharmaceutical and biomedical analysis.

[10]  M. Josefson,et al.  The synthesis of metoprolol monitored using Raman spectroscopy and chemometrics. , 2000, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[11]  Pavel Matousek,et al.  Transmission Raman spectroscopy as a tool for quantifying polymorphic content of pharmaceutical formulations. , 2010, The Analyst.

[12]  Y. Heyden,et al.  Influence of particle size on the quantitative determination of salicylic acid in a pharmaceutical ointment using FT-Raman spectroscopy. , 2007, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[13]  Mats Josefson,et al.  Quantification of an Active Substance in a Tablet by NIR and Raman Spectroscopy , 1998 .

[14]  P. Matousek,et al.  Raman Signal Enhancement in Deep Spectroscopy of Turbid Media , 2007, Applied spectroscopy.

[15]  R. Szostak,et al.  Quantitative determination of diclofenac sodium in solid dosage forms by FT-Raman spectroscopy. , 2008, Journal of pharmaceutical and biomedical analysis.

[16]  Jonas Johansson,et al.  Comparison of multivariate methods for quantitative determination with transmission Raman spectroscopy in pharmaceutical formulations , 2010 .

[17]  M. Blanco,et al.  Use of Near‐Infrared Spectroscopy for Off‐Line Measurements in the Pharmaceutical Industry , 2007 .

[18]  R. Szostak,et al.  Quantification of atorvastatin calcium in tablets by FT-Raman spectroscopy. , 2009, Journal of pharmaceutical and biomedical analysis.

[19]  R. J. Lehnert,et al.  The dependence of Raman signal intensity on particle size for crystal powders , 1996 .

[20]  Pavel Matousek,et al.  Deep Noninvasive Raman Spectroscopy of Turbid Media , 2008, Applied spectroscopy.

[21]  S. Wold,et al.  Orthogonal projections to latent structures (O‐PLS) , 2002 .

[22]  O. Svensson,et al.  Reaction monitoring using Raman spectroscopy and chemometrics , 1999 .

[23]  J. Rantanen,et al.  Raman spectroscopy for quantitative analysis of pharmaceutical solids , 2007, The Journal of pharmacy and pharmacology.

[24]  R. Barnes,et al.  Standard Normal Variate Transformation and De-Trending of Near-Infrared Diffuse Reflectance Spectra , 1989 .

[25]  T. Vickers,et al.  Effect of Powder Properties on the Intensity of Raman Scattering by Crystalline Solids , 2002 .

[26]  S. Byrn,et al.  Analysis of the Effect of Particle Size on Polymorphic Quantitation by Raman Spectroscopy , 2006, Applied spectroscopy.

[27]  P. Matousek,et al.  Bulk Raman Analysis of Pharmaceutical Tablets , 2006, Applied spectroscopy.

[28]  Michael D. Hargreaves,et al.  Pharmaceutical polymorphs quantified with transmission Raman spectroscopy , 2012 .

[29]  P. Matousek,et al.  Variation in the Transmission Near-Infrared Signal with Depth in Turbid Media , 2014, Applied spectroscopy.

[30]  K. Prebble,et al.  Some applications of near-infrared reflectance analysis in the pharmaceutical industry. , 1993, Journal of pharmaceutical and biomedical analysis.

[31]  N. Macleod,et al.  Characterisation of transmission Raman spectroscopy for rapid quantitative analysis of intact multi-component pharmaceutical capsules. , 2011, Journal of pharmaceutical and biomedical analysis.

[32]  Jonas Johansson,et al.  Quantitative Transmission Raman Spectroscopy of Pharmaceutical Tablets and Capsules , 2007, Applied spectroscopy.

[33]  Pavel Matousek,et al.  Dependence of Signal on Depth in Transmission Raman Spectroscopy , 2011, Applied spectroscopy.

[34]  C. Eliasson,et al.  Non-invasive quantitative assessment of the content of pharmaceutical capsules using transmission Raman spectroscopy. , 2008, Journal of pharmaceutical and biomedical analysis.

[35]  David Littlejohn,et al.  Comparison of the determination of a low-concentration active ingredient in pharmaceutical tablets by backscatter and transmission Raman spectrometry. , 2012, Analytical chemistry.

[36]  T. De Beer,et al.  In-line monitoring of a pharmaceutical blending process using FT-Raman spectroscopy. , 2004, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[37]  Dieter Oelkrug,et al.  Quantitative Raman spectroscopy in turbid matter: reflection or transmission mode? , 2013, Analytical and Bioanalytical Chemistry.

[38]  David Littlejohn,et al.  Effect of particle properties of powders on the generation and transmission of Raman scattering. , 2012, Analytical chemistry.