Application of ATR-MIR spectroscopy in the pilot plant—Scope and limitations using the example of Paracetamol crystallizations

The use of an access unit connected to a recirculation loop has shown to be a good solution for the integration of various process analytical technology (PAT) techniques in reactors of pilot plant or industrial scale without time and cost intensive modifications of the existing setup. The drawback of such a setup in crystallization processes can be the influence on the particle size (distribution) and morphology of the solid product induced by the recirculation. The access unit enables to monitor the concentration (supersaturation) of the model compound Paracetamol by the installation of an attenuated total reflectance Fourier transform-mid-infrared (ATR-FT-MIR) probe and therefore allows a rapid optimization of chemical and crystallization processes. The transferability of calibration models which were established at lab scale, was tested and evaluated in pilot plant experiments. It could be shown that a direct transfer of the peak integration model is possible under specific conditions. Effects such as water vapor in the spectrometer, movements of the fiber optic cable or minor encrustations of the sensor, however, can only be compensated by the application of indirect hard modeling (IHM). The method is capable of handling even non-constant external influences on the spectra as they are present in the pilot plant and therefore facilitate an inherent calibration transfer.