Infrared Spectroscopy for Process Analytical Applications

Infrared (IR) spectroscopy offers many unique advantages for measurements within an industrial environment, whether they are for environmental or for production-based applications. Historically, the technique has been used for a broad range of applications ranging from the composition of gas and/or liquid mixtures to the analysis of trace components for gas purity or environmental analysis. The instrumentation used ranges in complexity from simple filter-based photometers to optomechanically complicated devices, such as Fourier transform infrared (FTIR) spectrometers. Simple nondispersive infrared (NDIR) insttuments are in common use for measurements that feature well-defined methods of analysis, such as the analysis of combustion gases for carbon oxides and hydrocarbons. For more complex measurements it is normally necessary to obtain a greater amount of spectral information, and so either Ml-spectrum or multiple wavelength analyzers are required. 

Of the analytical techniques available for process analytical measmements, IR is one of the most versatile, where all physical forms of a sample may be considered - gases, liquids, solids and even mixed phase materials. A wide range of sample interfaces (sampling accessories) have been developed for infrared spectroscopy over the past 20 to 30 years and many of these can be adapted for either near-lme/at-lme production control or on-line process monitoring applications. For continuous on-line measurements applications may be limited to liquids and gases. However, for applications that have human interaction, such as near-line measurements, then all material types can be considered. For continuous measurements sample condition, as it exists within the process, may be an issue and factors such as temperature, pressure, chemical interfer-ants (such as solvents), and particulate matter may need to be addressed. In off-line applications this may be addressed by the way that the sample is handled, but for continuous on-line process applications this has to be accommodated by a sampling system. 

Process Analytical Technology 2e Edited by Katherine Bakeev 2010 John Wiley Sons, Ltd. 

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. 

Analytically, IR (FTIR) spectroscopy is unquestionably one of the most versatile techniques available for the measurement of molecular species in the laboratory today, and also for applications beyond the laboratory. A major benefit of the technique is that it may be used to study materials in almost any form, and usually without any modification all three physical states are addressed solids, liquids and gases. Also, it is a fundamental molecular property, and as such the information content can be considered to be absolute in terms of information content, and as such can be very diagnostic in terms of material purity and composition. Traces of impurities can be both uniquely detected and in most cases characterized. This is a very important attribute in a process analytical enviromnent. 

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Infrared Spectroscopy for Process Analytical Applications 169 Filter... 

NMR spectroscopy is relatively insensitive compared to optical spectroscopies such as Fourier transform infrared, requiring acquisitions of several minutes to obtain high signal-to-noise ratio spectra adequate for process analytical applications. The linear response and low sensitivity of NMR also prevents its use for observing very low level contaminants (<1000ppm) in complex mixtures. 

The objective of this chapter is to reduce the learning curve for the application of near-infrared (NIR) spectroscopy, or indeed any process analytical technology, to the chemical industry. It attempts to communicate realistic expectations for process analyzers in order to minimize both unrealistically positive expectations (e.g. NIR can do everything and predict the stock market ) and unrealistically negative expectations (e.g. NIR never works don t waste your money ). The themes of this chapter are value and... 

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... 

Infrared spectroscopy is a powerful alternative analytical technology for process monitoring which has found wide application as an off-line method in the chemical and food industries. The additional advantage over other methods is that in many circumstances it is possible to quantify a number of components simultaneously. 

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