Industrial applications of online monitoring of drying processes of drug substances using NIR

Drying is an important part of manufacturing processes in the chemical and pharmaceutical industry. The product quality often depends on the drying conditions and efficiency. Moreover, this unit operation frequently represents the bottleneck of the whole process. Therefore, online monitoring of the drying operation can lead to a significant improvement of the cycle time as well as to a reduction of the analytical work and costs. This paper demonstrates the effectiveness of NIR spectroscopy to control drying processes on an industrial scale. The examples shown in this study are realized using different kinds of dryers (filter dryer, paddle dryer, and spherical dryer) and various solvents (water and organic solvents). The spectral data are evaluated using multivariate calibration methods (partial least squares regression). These studies show that the solvent concentrations determined using NIR are in good agreement with the reference analyses. Moreover, the direct measurement in the powder allows stopping the drying process at a given residual solvent concentration (which is crucial in certain processes, e.g. to obtain specific hydrate forms). All together, the implementation of NIR for online monitoring of drying processes leads to a significant optimization of plant equipment utilization and to a higher throughput while reducing the risk of out-of-specifications batches.