NIR methods

Results found by the NIR method compared well with those obtained by the reference chromatographic procedures. The developed PLS/NIR method does not consume any solvent as no sample preparation is necessary, improving the laboratory efficiency without sacrifice the accuracy. 

For the extraction of rubber and rubber compounds a wide variety of solvents (ethyl acetate, acetone, toluene, chloroform, carbon tetrachloride, hexane) have been used [149]. Soxtec extraction has also been used for HDPE/(Tinuvin 770, Chimassorb 944) [114] and has been compared to ultrasonic extraction, room temperature diffusion, dissolution/precipitation and reflux extraction. The relatively poor performance of the Soxtec extraction (50% after 4h in DCM) as compared with the reflux extraction (95% after 2-4 h in toluene at 60 °C) was described to the large difference in temperature between the boiling solvents. Soxtec was also used to extract oil finish from synthetic polymer yam (calibration set range of 0.18-0.33 %, standard error 0.015 %) as reference data for NIRS method development [150]. 

Since the early 90s, noninvasive functional brain imaging of humans using NIR methods have been slowly gaining momentum despite existence of more established imaging modailties, such as PET, fMRI, and EEG. Part of the reason as stated previously, is because of its relatively high temporal resolution and its ability to monitor multiple tissue chromophores. The technique has been applied to adult as well as infant studies. NIR method is particularly suited for infant studies as the equipment, at least the CW kind, are minimally restraining, relatively safe, and portable [67]. Most neonatal studies focus on sensory stimulation such as visual, auditory and olfactory stimulations [69] [101] [89] [115] [6] [5], and cerebral disfunction [70, 71]. Our review will focus primarily on adult studies with some emphasis on defense and security applications. 

To summarize, current state of NIR research consists of two major groups of instrumentation (f) continuous wave and (2) time-resolved and frequency domain and two major groups of parameters assessed (f) slow responding hemodynamic (HbO and Hb) parameters and (2) fast response neuronal parameter. Assessing the fast response parameter requires high temporal resolution provided by NIR equipment. Such temporal resolutions are currently not possible using fMRI modality. Thus, a natural complementary relationship exists between fMRI and NIR methods, where fMRI can provide better spatial localization and NIR better temporal resolution. 

A preference of hemodynamic response is mainly due to better contrast-to-noise ratio and the ease of comparability with fMRI BOLD response which is inversely related to changes in Hb, over measurement of neuronal activity. However, measurement of the fast neuronal response can potentially benefit NIR methods by addressing the inherent pitfalls of MBLL assumptions in slow response measurements. Fast response, aside from being a direct measurement of neuronal activity, also has the potential to provide better spatial resolution. 

Selectivity, linearity, accuracy, precision, and robustness, as well as longterm drift, were addressed. The logic of the building of the equation used for prediction is detailed. The entire paper transcends a mere research paper and may serve as a blueprint for validation of NIR methods for bioprocessing. 

Finally, in the field of full-spectrum NIRS methods, Fourier transform near-infrared (FTIR) analyzers are included (Figure 5.5). FTIR techniques are predominant in mid-infrared spectroscopy because there are clear and absolute advantages for the FTIR analyzer in the mid-infrared compared with any other available technology. This arises because of the low power output of mid-infrared sources and the low specific detectivity... 

NIR methods are not the only on-line applications for blend monitoring FT-Raman " and laser induced fluorescence (LIF) have been utilized. Refer to Chapter 11 for a comprehensive review of LIF. As stated herein, NIRS is well established as an effective and advantageous means to deem blend homogeneity and blending end point, however there are circumstances in which NIR is insufficient. For example, LIF can be more suitable for blends with low drug load. Lai and Cooney illustrated in a lab-scale experiment that LIE yielded a limit of detection below 0.02% w/w for a given API. ... 

Borer et al. developed a NIR method to determine moisture in a highly hygroscopic product. Because the sample absorbed water very rapidly (0.02%/min), use of the Karl Fischer method as reference was very complicated. This led them to the choice of NIR spectroscopy, where the sample can be kept inside a sealed vial instead. Analyses were completed within a few seconds and the samples not exposed to ambient air at any time, which prevented moisture absorption and the ensuing determination errors. 

Tablets account for more than 80% of all pharmaceutical formulations therefore, the development and implementation of NIR methods for determining APIs in intact tablets is of a high interest with a view to assuring content uniformity and quality in the end product. Blanco et al developed an innovative strategy to prepare calibration samples for NIR analysis by using laboratory-made samples obtained by mixing the API and excipients in appropriate proportions and compacting the mixture at a pressure similar to that used industrially. This way of matching laboratory and production samples affords more simple and robust NIR methods which require the use of neither HPLC nor UV-vis spectroscopy as reference rather, reference values are obtained by weighing during preparation of the samples. The PLS calibration models thus constructed exhibited a good predictive ability with various production batches.

The results indicate that NIR does indeed have both the resolution (specificity) and the sensitivity needed for this application. The NIR method was successfully implemented in the plant, replacing the conventional GC method and allowing real-time control and optimization of the PDEB separation process. 

Cogdill, R. P, et al., (2005), Process analytical technology case study, Part I Feasibility studies for quantitative NIR method development, AAPS Pharm. Sci. Tech., 6, Article... 

In addition to the somewhat empirical and difficult development of NIR applications, thorough documentation must be produced. NIR methods have to comply with the current good manufacturing practice (cGMP) requirements used in the pharmaceutical industry. Various regulatory aspects have to be carefully considered. For example, NIR applications in classification, identification, or quantification require extensive model development and validation, a study of the risk impact of possible errors, a definition of model variables and measurement parameters, and... 

Cooper, P. J. "Developing and Testing On-Line NIR Methods for Process Control", 1985 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy. New Orleans, LA, Feb. 

Tablet hardness is a property that, when measured, destroys the sample. The destructive nature of the test, coupled with the variability of the test itself does not contribute to an incentive to test a large number of samples. Morisseau and Rhodes99 correlated the diffuse reflectance NIR spectra of tablets pressed at different pressures and subsequently tested the tablet hardness with an Erweka Hardness Tester. The tablet hardness, as predicted by the NIR method, was at least as precise as the laboratory test method. Kirsch and Drennen100 evaluated NIR as a method to determine potency and tablet hardness of Cimetidine tablets over a range of 1-20% potency and 107-kPa compaction pressure. Hardness at different potency levels was used to build calibration models using PCA/ principal component regression and a new spectral best-fit algorithm. Both methods provided acceptable predictions of tablet hardness.

The detection of molecular 02 by the NIR spectroscopic technique involves a measurement that is often described as a forbidden transition. Many molecules can absorb radiation (energy), enter a temporary excited or radiative state, and release energy (reradiation), which is called fluorescence. In the case of molecular Oz, there is such a transition that can be monitored in the NIR region of the spectrum near 760 nm. Therefore, 02 concentration can be measured in this "forbidden region" by NIR methods, such as using the TDLAS. 

The potential of the NIR method for the investigation of chemical transformations is demonstrated by a few examples of polymerization reactions. Fig. 6.2-24 shows a series of NIR spectra, measured in the second overtone region of the C -H stretching modes... 

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