NIR and Raman spectroscopies

Vibrational spectroscopy, in the form of mid-IR, NIR and Raman spectroscopy has been featured extensively in industrial analyses, both quality control (QC), process monitoring applications and held-portable applications [1-6]. The latter has been aided by the need for advanced instrumentation for homeland security and related HazMat applications. Next to chromatography, it is the most widely purchased classihcation of instrumentation for these measurements and analyses. Spectroscopic methods in general are favored because they are relatively straightforward to apply and to implement, are rapid in terms of providing results, and are often more economical in terms of service, support and maintenance. Furthermore, a single spectrometer or spectral analyzer, in a near-line application, may serve many functions, whereas chromatographs (gas and liquid) tend to be dedicated to only a few methods at best. 

P. de Peinder, M.J. Vredenbregt, T. Visser and D. de Kaste, Detection of Lipitor counterfeits A comparison of NIR and Raman spectroscopy in combination with chemometrics, J. Pharm. Biomed. Anal., 47, 688-694 (2008). 

Savolainen et al. investigated the role of Raman spectroscopy for monitoring amorphous content and compared the performance with that of NIR spectroscopy [41], Partial least squares (PLS) models in combination with several data pre-processing methods were employed. The prediction error for an independent test set was in the range of 2-3% for both NIR and Raman spectroscopy for amorphous and crystalline a-lactose monohydrate. The authors concluded that both techniques are useful for quantifying amorphous content however, the performance depends on process unit operation. Rantanen et al. performed a similar study of anhydrate/hydrate powder mixtures of nitrofurantoin, theophyllin, caffeine and carbamazepine [42], They found that both NIR and Raman performed well and that multivariate evaluation not always improves the evaluation in the case of Raman data. Santesson et al. demonstrated in situ Raman monitoring of crystallisation in acoustically levitated nanolitre drops [43]. Indomethazine and benzamide were used as model... 

NIR and Raman spectroscopy Properties affected by hydration state Skin surface water loss Elasticity... 

Jedvert, I. Josefson, M. Langkilde, F. Quantification of an active substance in a tablet by NIR and raman spectroscopy. J. Near Infrared Spectrosc. 1998, 6, 279-289. 

Figure 1.8. Some features and shortcomings of FTIR, NIR, and Raman spectroscopy. Italics indicate disadvantages.

This chapter reviews the use of spectroscopic methods for the quantitative analysis of pharmaceutical products. In recent years, there has been great progress made in the use of techniques such as NIR and Raman for real world pharmaceutical problems. USP chapters for NIR and Raman spectroscopy outline the requirements for equipment qualification and method validation. Because spectroscopic methods for quantitative analysis often involve the use of MVA and chemometrics, the approaches for method validation are somewhat different than that for traditional chromatographic methods. 

R. P. Ortiz, M. C. Ruiz Delgado, J. Casado, V. Hernandez, O.-K. Kim, H. Y. Woo, J. T. Ldpez Navarrete, Electronic modulation of dithienothiophene (DTT) as jr-center of D-rr-D chromophores on optical and redox properties Analysis by UV-Vis-NIR and Raman spectroscopies combined with electrochemistry and quantum chemical DPT calculations, J. Am. Chem. Soc, 126, 13363-13376 (2004). 

Over the past years MIR, NIR, and Raman spectroscopy have been further developed to a point where each technique can be considered a potential candidate for industrial quality-control and process-monitoring applications. However, adding up the specific advantages and disadvantages of the individual techniques, NIR spectroscopy is certainly the most flexible and advanced alternative. 

In principle, all kinds of spectroscopic techniques lend themselves to on-line measurements. Only a very few are practical. Although low-field NMR has been used to measure various material properties by applying empirical relationships, NMR is still not a realistic proposition for on-line measurements. Ironically, ETIR spectroscopy suffers from too much sensitivity. Typically, good spectra can be obtained only from very thin polymeric films (or solutions). Attenuated total reflection (ATR) probes, in which only a fraction of the IR light penetrates a very short distance into the sample, reduce the problem of excessive sensitivity. However, they aggravate the problems of variations in the baseline and nonlinear response. The latter problem also obstructs the use of UV spectrometry for monitoring polymerization reactions. Of the remaining options, near-infrared (NIR) and Raman spectroscopy are the most attractive. 

It must also be noted that multiple PAT analyzers can be used on a single unit operation to understand the process. For example, Aaltonen et used in-line Raman spectroscopy and in-line NIRS to monitor the dehydration of MT in a lab-scale fluid bed dryer. A PLS model was generated to quantify the solid-state transformation using Raman spectra while water removal was monitored using NIRS. This proved to be an effective combination because physical and chemical information were monitored and extracted by way of NIRS and Raman spectroscopy, respectively. Such combinations of process analyzers offer enhanced capabilities to improve process understanding and control. 

Infrared (IR), near-infrared (NIR), and Raman spectroscopy have been successfully used for quantitative and qualitative analysis of polymer films. These methods leverage the fact that vibrational spectra are very sensitive to polymer structure and the strength of chemical bonds of functional groups. NIR spectroscopy has several practical advantages in polymer film analysis, including nondestructive and... 

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