Terahertz Frequency Domain Sensing for Fast Porosity Measurement of Pharmaceutical Tablets

TL;DR

This paper demonstrates that terahertz frequency-domain sensing provides a rapid, non-destructive, and sensitive method for measuring porosity in pharmaceutical tablets, with potential for in-situ manufacturing applications.

Contribution

It introduces a novel application of THz-FD technique for in-situ porosity measurement of tablets, correlating effective refractive index with porosity, and verifying results with microscopy.

Findings

THz-FD technique is highly sensitive to tablet design factors.

Filler particle size and compaction force significantly affect porosity.

The method enables fast, non-destructive, in-situ porosity assessment.

Abstract

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.