Application of Ultrasound Measurements as PAT Tools for Industrial Crystallization Process Development of Pharmaceutical Compounds

Within this work, 12 different pharmaceutical compounds were analyzed by the single-frequency ultrasound measurement technique for its applicability to determine concentrations, as an important process parameter during crystallization processes, or to determine the metastable zone widths, as an important precondition for the development of crystallization processes. The results were compared to the applicability of inorganic and nonpharmaceutical compounds that have been discussed in the literature. It was found that according to the change of ultrasound velocity and adiabatic compressibility, a grouping of compounds can be derived. From this grouping it can be concluded that some organic compounds and especially inorganic compounds show an excellent applicability for concentration determination, while the application for pharmaceutical compounds is most often limited. Furthermore, a cost- and time-efficient possibility is shown for the integration of this technique in a pilot-plant-scale setup. A direct transferability of calibration models developed at the laboratory scale was found as long as the influence of undissolved air/gas was low in the pilot-plant setup.