Rapid in-line Process Analysis of Physical Tablet Properties with THz-TDS

Process analysers are integral to the FDA's Process Analytical Technology framework, playing a vital role in enhancing drug product quality. Innovative analytical methods in tablet manufacturing predominantly focus on chemical attributes, such as the API content. Terahertz time-domain spectroscopy (THz-TDS) is a fast and non-destructive method that shows promise in bridging the gap for in-process monitoring of physical tablet properties. It is based on the time-of-flight measurement of terahertz (10^12 Hz) pulses. This time-of-flight-principle is used in-line in a small-scale tableting process to extract tablet height and mass with minimal errors below 1 %. The extracted parameters can further serve as input for a calibration-based evaluation of tablet porosity, breaking force, and disintegration time yielding suitable errors. The presented approach demonstrates a high potential for process control and real-time release testing as modern equipment provides speeds that match industrial tableting machines and thus enable the monitoring of every produced tablet.