Process Raman spectroscopy, analytical method Applications

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). 

IR is one of three forms of vibrational spectroscopy that is in conunon use for process analytical measurements the other two being near-lR (NIR) and Raman. Each one of these techniques has its pros and cons and the ultimate selection is based on a number of factors ranging from sample type, information required, cost and ease of implementation. The sample matrix is often a key deciding factor. NIR has been the method of choice for many years within the pharmaceutical industry, and sample handling has been the issue, especially where solid products are involved. IR is not particularly easy to implement for the continuous monitoring of solid substrates. However, often there is no one correct answer, but often when the full application is taken into account the selection becomes more obvious. In some cases very obvious, such as the selection of IR for trace gas analysis - neither NIR nor Raman is appropriate for such applications. 

One indication of the developing interest in PATs in the pharmaceutical area is the number of book chapters and review articles in this field that have appeared in the last few years. Several chapters in The Handbook of Vibrational Spectroscopy3 are related to the use of various optical spectroscopies in pharmaceutical development and manufacturing. Warman and Hammond also cover spectroscopic techniques extensively in their chapter titled Process Analysis in the Pharmaceutical Industry in the text Pharmaceutical Analysis.4 Pharmaceutical applications are included in an exhaustive review of near-infrared (NIR) and mid-infrared (mid-IR) by Workman,5 as well as the periodic applications reviews of Process Analytical Chemistry and Pharmaceutical Science in the journal Analytical Chemistry. The Encyclopedia of Pharmaceutical Technology has several chapters on spectroscopic methods of analysis, with the chapters on Diffuse Reflectance and Near-Infrared Spectrometry particularly highlighting on-line applications. There are an ever-expanding number of recent reviews on pharmaceutical applications, and a few examples are cited for Raman,7 8 NIR,9-11 and mid-IR.12... 

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