THz-TDS transflection measurements as a process analyser for tablet mass

Tablet content and content uniformity are essential for the market release of the drug product. For tablets, content and uniformity are determined by the weight ratio of active pharmaceutical ingredient in the tablet and the tablets' total mass. Novel process analytical technology tools for the control of the ratio of the active pharmaceutical ingredient have been proposed and implemented, but more robust, sensitive, and fast sensors for the control of tablet mass are desirable. In the presented study terahertz time-domain spectroscopy (THz-TDS) is proposed as a potential process analyser for tablet mass. THz-TDS is based on pulsed terahertz signals, which are mapped in the time-domain. Thus, the signal amplitude and arrival time are recorded. THz-TDS measurements of a tablet with a reflection setup result in two signals - a frontside reflection and a backside transflection. The presented study demonstrates that an increase in the tablet mass results in an increase in the time delay of the backside transflection. This is a result of the high refractive index of the solid fraction compared to air. It is suggested that the time delay of the transflection can be used as an indirect measure of tablet mass for which root mean squared errors of around 1 mg were found. The potential to measure tablets at high acquisition rates (50 Hz) is explored and considered feasible. Additionally, it has been demonstrated in previous work that the time delay of the frontside reflection allows a simultaneous assessment of the tablet height. The presented methodology opens the possibility of in-line monitoring of tablet mass as part of a content and content uniformity strategy at high sampling rates in the production environment. Further, as tablet height and mass can be assessed simultaneously, monitoring and control of the compression process based on a comprehensive assessment of physical tablet attributes can also be envisioned.