Terahertz sensing for pharmaceutical applications

Doctoral thesis, 2023

Pharmaceutical tablets are manufactured through the compaction of powder blends or granules in batch or continuous processes. In continuous manufacturing, real-time assurance of quality becomes essential to ensure that the final product meets the quality standards approved by manufacturers and regulatory authorities. Process analytical methods used for real-time monitoring and control should be rapid, non-destructive, and suitable to be conducted in the manufacturing area. This thesis demonstrates the terahertz frequency domain (THz-FD) technique, based on all-electronic solutions, as a fast, sensitive, and non-destructive sensing technique, with the advantage of a reasonable compromise between deep penetration depth and high spatial resolution, high dynamic range, and miniaturization capabilities. In this study, the THz-FD technique was explored to monitor the key physical properties such as tablet density and porosity through effective refractive index using a vector network analyser. In addition, taking advantage of the lower scattering effect of the THz region compared to higher frequencies, the feasibility of terahertz frequency domain spectroscopy (THz-FDS) combined with multivariate analysis to quantify drug content and tablet density was explored. As the quality of the tablets is highly impacted by the powder flow during manufacturing processes, it is beneficial to build quality assurance before the tableting process. In the last study, the capability of a terahertz frequency-modulated continuous wave (FMCW) radar was for the first time explored to characterise the powder flow dynamics in manufacturing processes. The velocity and density variations of falling powder streams in a vertical tube were non-invasively measured, using a 340-GHz radar instrument with a deep penetration depth through the powder flow and a sample volume resolution in the order of a few cubic centimeters.

In conclusion, it was demonstrated that the THz-FD technique and terahertz FMCW radar are highly promising as non-invasive process analytical tools for real-time quality monitoring of pharmaceutical powders and tablets.