Near-infrared Spectroscopic Process Analysis

Principles and Characteristics The role of quality is increasingly being recognised in chemical production. From an analytical chemical point of view, in most cases the goal in continuous processes is to keep the process composition steady at around the optimum physical and chemical conditions. Uniform quality is a requirement with many other aspects too, such as legal obligations, economical production, environmental protection, and plant safety. All of these require that the composition of various products be kept stable [113]. Consequently, reliable, selective, and sensitive process analysers are much needed. 

As the purpose of the analysis is to use the data to control the process timing considerations are vital. The response time of a complete control system (to correct for any change in the concentration of the product) includes the time of sampling, analysis, calculation of the concentration and the amount 

Non-destructive optical analysis offers an instantaneous in-line measurement of concentration. NIR spectroscopy fits well into the list of technologies suitable for process analysis it is fast, precise and non-destructive. When used properly it is also accurate for macro-analysis of major chemical composition parameters or contaminants. Its methodology includes the use of quantitative and qualitative chemometric techniques. In near-infrared, due to the generally much lower absorption coefficients of most combination and overtone bands with respect to the fundamental vibrations of mid-IR, undiluted materials can be analysed in situ in many cases through reasonable path lengths. Process control using NIRS has developed as from about 1980. 

Unlike a single wavelength UV monitor, or a refractive index monitor, a NIR analyser is not a single parameter measurement device. In a process situation, NIR analysis is carried out in a manner similar 

Balke et al [116] have discussed the design of melt-at-die, melt-in-barrel and strand interfaces be- 

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T. Sato, H. Abe, S. Kawano, G. Ueno, K. Suzuki, M. Iwamoto. Near-infrared spectroscopic analysis of deterioration indices of soybeans for process control in oil millmg plant. JAm Oil Chem Soc 71 1049-1055, 1994. 

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... 

In a pharmaceutical plant that has embraced PAT, the testing protocol for the process looks very different to that of a plant that still carries out off-line assays (Figure 9.7). Spectroscopic analysis is the most popular method especially for dry products such as raw materials and drug powders. Near infrared (NIR) and Raman, due to the noncontact nature of these techniques, are prevalent. All of the various types of process analysers are discussed in the following sections. 

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]). 

Spectroscopic sensors, in combination with multivariate data analysis, will often win the competition for most favorable process analyzer as compared to other during-process measurements. The most commonly used spectroscopic techniques for process monitoring are ultraviolet-visual absorption (UV-vis), near-infrared (NIR) and infrared (IR) absorption,... 

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... 

Infrared spectroscopy performed both in the mid-IR [70] and near-IR [71] provides the potential of rapid determination with little or no sample preparation. Raman spectroscopy also has demonstrated capability for pharmaceutical analysis [72], Vibrational spectroscopic techniques are effective for compositional and structural characterization, as well as quantitation. However, bulk spectrosocpy is ineffective for measuring the spatial distribution and architecture of actives, which are heterogeneously distributed within intact tablets. Raman chemical imaging equipped with multivariate image processing capabilities is a powerful approach to the analysis of pharmaceutical tablet architecture. 

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