Vibrational spectroscopic methods, such as FTIR-, NIR- and Raman-spectroscopy are the weapon of choice for the in-line monitoring. Even though, the three spectroscopic methods are similar, they have plenty of differences. While FTIR-spectroscopy is well known, and has established its space in the industry, the in-line implementation of the technique is not as straightforward as for the other techniques. In most cases FTIR-spectroscopy requires sample preparation, but it can be avoided with ATR-probes (Attenuated Total Reflection). We have implemented FTIR in-line monitoring for synthetic chemical reaction monitoring, control and end-point analysis in organic solvents with ATR-probe.
NIR-spectroscopy can be easily applied in many operations with reflection probes, and the transmission probes are capable of fast measurements of the products, but complicated data analysis is required compared to the other two spectroscopic method. NIR-spectroscopy proved useful for numerous solid state monitoring applications with reflection probe. Monitoring of API content, water content and even PET foaming has been achieved in our research group. Transmission probe was applied for off-line content uniformity analysis for tablets, and also for dissolution modeling.
Raman-spectroscopy can be considered a modern technique. It is the most expensive method due to the low chance of Raman-scattering and the high dependency on monochromatic light source. However, the technique has developed into a commercially available vibrational spectroscope which is fast, easily applicable, non-destructive and allows reliable qualitative and quantitative analysis even in low concentrations. The Raman spectrum is very similar to the FTIR-spectrum, but different selection rules apply to the two methods. Due to these selection rules, the Raman-spectroscopy is not sensitive to the water content, therefore this makes this vibrational spectroscopic method applicable even in aqueous solutions. Raman-spectroscopy was useful for process monitoring in solid state applications, such as powder blending, tableting, electrospinning, but our research group also applied Raman-spectroscopy for the monitoring and control of crystallization and for the analysis and control of synthetic reactions in different solutions.
