Process Raman spectroscopy, analytical method

Identifying pharmaceuticals, whether APIs or excipients used to manufacture products, and the end products themselves is among the routine tests needed to control pharmaceutical manufacturing processes. Pharmacopoeias have compiled a wide range of analytical methods for the identification of pharmaceutical APIs and usually several tests for a product are recommended. The process can be labor-intensive and time-consuming with these conventional methods. This has raised the need for alternative, faster methods also ensuring reliable identification. Of the seven spectroscopic techniques reviewed in this book, IR and Raman spectroscopy are suitable for the unequivocal identification of pharmaceuticals as their spectra are compound-specific no two compounds other than pairs of enantiomers or oligomers possess the same IR... 

Sampling in surface-enhanced Raman and infrared spectroscopy is intimately linked to the optical enhancement induced by arrays and fractals of hot metal particles, primarily of silver and gold. The key to both techniques is preparation of the metal particles either in a suspension or as architectures on the surface of substrates. We will therefore detail the preparation and self-assembly methods used to obtain films, sols, and arrayed architectures coupled with the methods of adsorbing the species of interest on them to obtain optimal enhancement of the Raman and infrared signatures. Surface-enhanced Raman spectroscopy (SERS) has been more widely used and studied because of the relative ease of the sampling process and the ready availability of lasers in the visible range of the optical spectrum. Surface-enhanced infrared spectroscopy (SEIRA) using attenuated total reflection coupled to Fourier transform infrared spectroscopy, on the other hand, is an attractive alternative to SERS but has yet to be widely applied in analytical chemistry. 

Fundamental questions related to the electronic configuration of the open or colored forms and the number and structures of the photomerocyanine isomers are considered on the basis of the results of continuous-wave (stationary) and time-resolved (picosecond, nanosecond, and millisecond) Raman experiments. For spironaphthoxazine photochromic compounds, the Raman spectra may be attributed to the TTC (trans-trans-cis) isomer having a dominant quinoidal electronic configuration. Surface-enhanced resonance Raman spectroscopy (SERRS) is demonstrated as a new analytical method for the study of the photodegradation process in solution for nitro-BIPS derivatives. The development of this method could lead to the identification of the photoproducts in thin polymer films or sol-gel matrices and ultimately to control of degradation. 

The composition of a polymeric material is of interest throughout its useful life from process stream to product fabrication, and finally to post-consumer recycling. It is desirable to know not only what types of materials are present, but also their relative concentrations. In many cases, Raman spectroscopy can provide a quick, convenient and relatively inexpensive alternative conventional analytical method for performing these types of determinations (266). 

Depending on the type of reaction and analytes to be investigated, different optical spectroscopic methods are available [7]. Typically UV-Vis, near-infrared (NIR), mid-infrared (MIR) and Raman spectroscopy are the most popular in process analysis (see Table 6.1) [8]. Other, emerging in-line methods such as fluorescence and chemiluminescence spectroscopy are still of minor importance in process technologies and will be not discussed here (for additional information, see [9]). 

Time-resolved resonance Raman spectrometry is a technique that allows collection of Raman spectra of excited state moleeules. It has been used to study intermediates in enzyme reactions, the spectra of carotenoid excited states, ultrafast electron transfer steps, and a variety of other biological and bioinorganic processes. Time-discrimination methods have been used to overcome a major limitation of resonance Raman spectroscopy, namely, fluorescence interference either by the analyte itself or by other species present in the sample. 

Our work has been predicated on the premise that Raman spectroscopy has the potential to play a significant role in the next generation of analytical methods, in-line analysis without treatment of the sample. To fulfill this promise, it is necessary to develop an instrument that has the robustness, accuracy, and low cost that a process control instrument must have. In the above paragraphs, questions regarding both abscissa and ordinate characterization are discussed. Two major aspects have been considered. 

As it is common in the Raman scattering process to observe Raman band intensities of ca. 10 of the incident photons (UV, VIS, NIR) provided by a monochromatic laser source, Raman spectroscopy is an inherently insensitive analytical method that usually requires molecular concentrations of >0.01 M. Raman spectroscopy probably represents the single largest application of laser spectroscopy in industrial analysis and is being used in industry only as from the 1980s for the analysis of a wide range of materials, mainly solids. Raman spectroscopy is... 

Over the last three decades, in particular gas chromatographs, electrochemical detectors and gas analysers have found their way to the process environment. Most recently, various analytical techniques that were formerly only used in the laboratory have become suitable for implementation in manufacturing. Examples are UVA IS absorption spectroscopy, near-IR spectroscopy, refractive index measurements and more recently mid-lR spectroscopy, Raman spectroscopy, pulse NMR and mass spectrometry. In particular, the number of spectroscopic applications has increased, sometimes replacing more established measurement methods (like GC or gas analysers). In addition, other traditional laboratory/off-line methods are now moving towards in-process applications e.g. rheometry and XRF). 

In a broad sense, spectroscopic methods applied in process analytics comprise widely used techniques like UVA IS, mid-IR, NIR, NMR and XRF, and less frequently used ones, such as Raman spectroscopy, fluorescence, chemiluminescence, acoustic emission and dielectric specfloscopy. Upcoming in-process analysis techniques are 2D-fluorescence, and laser absorption specfloscopy (LAS) with tuneable lasers and ppm level sensitivity. The availability of mini-spectrometers (e.g. UVA IS/NIR) is not highly relevant in plant environments where safety is of primary concern. 

There are several methods available to monitor emnision polymerization reactions, such as gravimetric and GC analysis, nonetheless, they are time consuming. Others snch as densitometry, ultrasound velocity, and calorimetry can be applied for online analysis, but they are ledpe specific and are unable to discriminate between monomers in a copolymerization. More recently, advanced analytical techniqnes such as Fourier transform infrared spectroscopy (FT IR) and Raman spectroscopy have been developed for online and in-line monitoring of emulsion polymerization processes. The major drawback of the near-infrared (NIR) spectroscopic... 

The Raman spectroscopy provides the opportunity to investigate a sample in a noninvasive and nondestructive way. It is as a nonsensitive analytical method towards water and air and can be used for online process monitoring. The intensity of the bands obtained is dependent on the electron density, which makes this method interesting for polymerization reactions where the intensity of the carbon-carbon-double bond decreases over time. 

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