Raman pharmaceutical product

C. Eliasson and P. Matousek, Noninvasive authentication of pharmaceutical products through packaging using spatially offset Raman spectroscopy, Arml Chem., 79, 1696-1701 (2007). 

Abstract This chapter reviews emerging techniques for deep, non-invasive Raman spectroscopy of diffusely scattering media. As generic analytical tools, these methods pave the way for a host of new applications including non-invasive disease diagnosis, chemical identification and characterisation of pharmaceutical products. 

Raman is not immune from experimental difficulties. One of the major problems associated with using Raman spectroscopy to analyse pharmaceutical products is fluorescence [32]. This arises from the emission of a photon during relaxation to the electronic ground state and may be caused by the drug itself, a low-level impurity, excipients in the formulated product or... 

Fig. 19.3. Representative micro-Raman spectra of single bacterial cells belonging to different species and strains that are predominantly present in pharmaceutical production in case of microbial contamination...

Cover Figure Raman spectra of two polymorphs of Cimetidine are shown on the cover Cimetidine is a pharmaceutical product that has six polymorphic forms and each form has a distinctive Raman spectrum as shown in Figure 4 25 of Chapter 4 (with permission of Ref 47). The particular polymorphic or crystalline form of a compound can be very important since the bio- availability and patent positions often depend upon the form Raman spectra can be used to easily identify the polymorphic form. 

I 7 7 Raman Spectral Imaging on Pharmaceutical Products 11.2.3.3 Spectral Resolution and Detection Limit... 

Raman hyperspectral imaging provides an excellent means of characterizing the chemical and spatial composition of pharmaceutical products. The most important point when performing successful Raman hyperspectral imaging is to understand the intertwined relationship between spectroscopy and imaging, as the spectral quahty-and especially the spectral resolution and SNR-will have a direct impact on the spatial quality produced. 

The properties of the transmission Raman geometry are well suited to the requirements of pharmaceutical production lines, thus underlining the potential of this method to displace existing NIR absorption spectroscopy in applications where a higher chemical specificity is required. However, further studies are required to establish the technique s sensitivity limits and to validate its potential. 

Abstract Spectroscopic methods such as NIR, Fourier transform infrared, and Raman are becoming increasing important in pharmaceutical research and manufacturing. This chapter reviews both quantitative and qualitative applications of spectroscopic analysis for pharmaceutical products. Several applications of these technologies to stability testing are discussed. 

Spectroscopic methods can provide fast, non-destructive analytical measurements that can replace conventional analytical methods in many cases. The non-destructive nature of optical measurements makes them very attractive for stability testing. In the future, spectroscopic methods will be increasingly used for pharmaceutical stability analysis. This chapter will focus on quantitative analysis of pharmaceutical products. The second section of the chapter will provide an overview of basic vibrational spectroscopy and modern spectroscopic technology. The third section of this chapter is an introduction to multivariate analysis (MVA) and chemometrics. MVA is essential for the quantitative analysis of NIR and in many cases Raman spectral data. Growth in MVA has been aided by the availability of high quality software and powerful personal computers. Section 11.4 is a review of the qualification of NIR and Raman spectrometers. The criteria for NIR and Raman equipment qualification are described in USP chapters <1119> and < 1120>. The relevant highlights of the new USP chapter on analytical instrument qualification <1058> are also covered. Section 11.5 is a discussion of method validation for quantitative analytical methods based on multivariate statistics. Based on the USP chapter for NIR <1119>, the discussion of method validation for chemometric-based methods is also appropriate for Raman spectroscopy. The criteria for these MVA-based methods are the same as traditional analytical methods accuracy, precision, linearity, specificity, and robustness however, the ways they are described and evaluated can be different. 

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. 

Virtually all the active substances in pharmaceutical products are synthesized in solution. The reactions are mostly followed by wet methods or chromatography. This is yet another case in which an ATR (MIR), fiber optic probe (MIR/NIR/Raman), or window (NIR/Raman) into the reaction vessel would allow for real-time analyses. 

In many pharmaceutical products, the formulated end products contain dyes, additives, excipients, binders, active materials, and an identification mark. The active materials are often crystalline with a high Raman-scattering cross section, whereas the excipients generally have a lower Raman cross section and many exhibit low levels of fluorescence. In addition, the dyes and the identification mark tend to fluoresce under visible excitation. Thus, FT-Raman spectroscopy has proved itself in formulated product analysis, whereas dispersive Raman spectroscopy with visible excitation can be successfully employed for monitoring active-material manufacturing. 

The final example cited in this subsection, the use of Raman spectroscopy to the study of pharmaceuticals, is in the area of identification and quantitation of materials in finished pharmaceutical products and formulations. A host of authors, using everything from bench-top laboratory analyzers, microprobes, and fiber-optics sampling devices have demonstrated the use of Raman spectroscopy for identification and quantification [117-122]. Limits of detection and reproducibility for many of the materials studied were reported. 

Most chemists tend to think of infrared (IR) spectroscopy as the only form of vibrational analysis for a molecular entity. In this framework, IR is typically used as an identification assay for various intermediates and final bulk drug products, and also as a quantitative technique for solution-phase studies. Full vibrational analysis of a molecule must also include Raman spectroscopy. Although IR and Raman spectroscopy are complementary techniques, widespread use of the Raman technique in pharmaceutical investigations has been limited. Before the advent of Fourier transform techniques and lasers, experimental difficulties limited the use of Raman spectroscopy. Over the last 20 years a renaissance of the Raman technique has been seen, however, due mainly to instrumentation development. 

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