Terahertz Frequency Domain Sensing for Fast Porosity Measurement of Pharmaceutical Tablets

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 behavior 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

Small Variation of Active Pharmaceutical Ingredient Concentration Can Be Observed with THz Frequency Domain Spectroscopy

Terahertz frequency-domain spectroscopy (THz-FDS) has been employed to study the result of the variation of active pharmaceutical ingredients (API) on the effective refractive index of pharmaceutical tablets. A quasi-optical set-up with four off-axis parabolic mirrors was used to measure the effective refractive index of tablets in the frequency range of 500-750 GHz. It was observed that a small variation in API concentration can be detected using accurate measurements of the complex transmission coefficients. As a result, THz-FDS reveals to be an effective technique in monitoring the physical properties of pharmaceutical tablet

Monitoring the Porosity of Pharmaceutical Tablets Using THz Frequency Domain Spectroscopy

In this paper, terahertz frequency domain spectroscopy (THz-FDS) in transmission mode has been employed to study the impact of design parameters of tablets such as initial particle size, drug concentration and compaction force, on their porosity. The complex transmission coefficient S21 of 69 tablets were measured using a vector network analyzer in the frequency range of 500-750 GHz. The results show that excipient particle size and compaction force have significant effects on the pore structure of the tablets and THz-FDS reveals to be a very promising tool in monitoring the porosity of pharmaceutical tablets