Moritz Anuschek ^a,b, Thomas Kvistgaard Vilhelmsen ^b, J. Axel Zeitler ^c, Jukka Rantanen ^a

^a Department of Pharmacy, University of Copenhagen, Copenhagen, Denmark

^b Novo Nordisk A/S, ET Oral Product Development, Måløv, Denmark

^c Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK

Purpose. Terahertz time-domain spectroscopy (THz-TDS) was used for the simultaneous, in-line assessment of tablet height and mass as well as porosity, breaking force, and disintegration time.

Methods. A multicomponent formulation was compressed (XP1, Korsch AG, Germany) at 50 tablets/s. THz-TDS (LX, TeraView Ltd., UK) spectra of tablets were acquired in reflection with an in-line sampling-interface. Calibration was carried out off-line. Reference values were obtained by sampling (every 30 s) and conventional pharmacopoeia methods.

Results. THz-TDS measurement of a tablet results in two signals. 1.) A reflection from the front side, for which the arrival time correlates with the surface-to-probe distance, and hence tablet height. 2.) A transreflection of the back side for which the travel distance is fixed (i.e. constant interface-to-probe distance) and the arrival time thus depends on the material amount (i.e. the tablet mass) in the signal’s path.
This concept was utilised for the in-line measurement of tablet height (RMSEP = 0.014 mm) and mass (RMSEP = 0.7 mg) (see Figure 1) for which the estimates followed the off-line reference results. Measured values of tablet height and mass could further be used to calculate tablet porosity (RMSEP = 0.35 %). Based on pre-established calibration functions, acquired tablet properties allowed for an additional determination of the breaking force (RMSEP = 6.1 N) and disintegration time (RMSEP = 3.5 s).

Figure 1 Tablet height (H) and mass (m) as a function of the process time, measured in-line with THz-TDS based on pre-established calibration models. Reference values were determined off-line based on manually sampled data.

Conclusions. The presented methodology allowed for an in-line assessment of physical attributes of tablets, immediately after compression (< 2 s) and with a high sampling rate (1.4 tablets/s).