In-line monitoring of tablet compression with terahertz time-domain spectroscopy for physical tablet characteristics

Process analysers integrated in process analytical technology (PAT) systems are now well-established in the pharmaceutical industry. These sensors play a crucial role in advancing manufacturing science by enabling robust process designs aligned with Quality by Design principles and continuous manufacturing practices. Although tablets are the most important drug delivery platform, limited attention has been given to the development of process analysers for tablet properties beyond the chemical composition. In this study, THz-TDS for the in-line monitoring of physical properties in a lab-scale compression process is reported, as well as contrasted with other existing sensors used for this purpose. The calibration, in-line application, and real-world benefits of the proposed procedure are discussed. THz-TDS enabled accurate monitoring of placebo tablets with low root mean squared errors of prediction (RMSEP) of tablet thickness (RMSEP = 0.013 mm), mass (RMSEP = 0.63 mg), porosity (RMSEP = 0.36 %), breaking force (RMSEP = 13.3 N), and disintegration time (RMSEP = 3.5 s) of placebo tablets with an average measurement speed of 1.5 s per tablet. Future implementation will enable a more robust process design based on in-depth knowledge through frequent property determination, real-time monitoring and control of the compression process, and ultimately real-time release testing of thickness, porosity, mass, mechanical strength, and the disintegration time of the end-product.