  Porosity is an important property of pharmaceutical tablets since it may
affect tablet disintegration, dissolution, and bio-availability. It is,
therefore, essential to establish non-destructive, fast, and compact techniques
to assess porosity, in-situ, during the manufacturing process. In this paper,
the terahertz frequency-domain (THz-FD) technique was explored as a fast,
non-destructive, and sensitive technique for porosity measurement of
pharmaceutical tablets. We studied a sample set of 69 tablets with different
design factors, such as particle size of the active pharmaceutical ingredient
(API), Ibuprofen, particle size of the filler, Mannitol, API concentration, and
compaction force. The signal transmitted through each tablet was measured
across the frequency range 500-750 GHz using a vector network analyzer combined
with a quasi-optical set-up consisting of four off-axis parabolic mirrors to
guide and focus the beam. We first extracted the effective refractive index of
each tablet from the measured complex transmission coefficients and then
translated it to porosity, using an empirical linear relation between effective
refractive index and tablet density. The results show that the THz-FD technique
was highly sensitive to the variations of the design factors, showing that
filler particle size and compaction force had a significant impact on the
effective refractive index of the tablets and, consequently, porosity.
Moreover, the fragmentation behaviour of particles was observed by THz porosity
measurements and was verified with scanning electron microscopy of the
cross-section of tablets. In conclusion, the THz-FD technique, based on
electronic solutions, allows for fast, sensitive, and non-destructive porosity
measurement that opens for compact instrument systems capable of in-situ
sensing in tablet manufacturing.
