Terahertz-Based Porosity Measurement of Pharmaceutical Tablets: a Tutorial

Abstract

Porosity, one of the important quality attributes of pharmaceutical tablets, directly affects the mechanical properties, the mass transport and hence tablet disintegration, dissolution and ultimately the bioavailability of an orally administered drug. The ability to accurately and quickly monitor the porosity of tablets during manufacture or during the manufacturing process will enable a greater assurance of product quality. This tutorial systematically outlines the steps involved in the terahertz-based measurement method that can be used to quantify the porosity of a tablet within seconds in a non-destructive and non-invasive manner. The terahertz-based porosity measurement can be performed using one of the three main methods, which are (i) the zero-porosity approximation (ZPA); (ii) the traditional Bruggeman effective medium approximation (TB-EMA); and (iii) the anisotropic Bruggeman effective medium approximation (AB-EMA). By using a set of batches of flat-faced and biconvex tablets as a case study, the three main methods are compared and contrasted. Overall, frequency-domain signal processing coupled with the AB-EMA method was found to be most suitable approach in terms of accuracy and robustness when predicting the porosity of tablets over a range of complexities and geometries. This tutorial aims to concisely outline all the necessary steps, precautions and unique advantages associated with the terahertz-based porosity measurement method.

Terahertz time-domain spectroscopy for powder compact porosity and pore shape measurements: An error analysis of the anisotropic bruggeman model

“…The traditional Bruggeman model is a commonly used approach for EMA that was developed in the early 20th century by Bruggeman (1935) . It describes the dielectric properties of a composite material (the so-called effective medium) by combining the individual dielectric properties, , of the volume fractions occupied by the isolated materials where the minor fraction, the inclusions, are assumed to be of spherical shape and the major fraction forms a continuous phase ( Bruggeman, 1935 ; Bawuah et al, 2020 ). This formalism was later developed further by including a depolarisation factor into what is now known as the AB-EMA, where inclusions are spheroids with their polar axis aligned parallel to the propagation direction of the electromagnetic field ( Jones and Friedman, 2000 ).…”

“…For multiple solid components it was demonstrated that the dielectric properties of the different solid components can be combined into a single solid fraction with the average dielectric properties ( Bawuah et al, 2020 ).…”

“…Terahertz time-domain spectroscopy (THz-TDS) has been suggested as a fast and non-destructive technique for porosity and pore shape measurements ( Bawuah et al, 2016b ; Bawuah and Peiponen, 2016 ; Bawuah et al, 2016c ). The use of non-ionising radiation and the advantage of fast (sub-second) measurement acquisition makes it ideal for in-line or at-line control applications ( Bawuah et al, 2020 ). Furthermore, most pharmaceutical excipients are at least semi-transparent at terahertz frequencies allowing for measurements in transmission mode ( Zeitler et al, 2007 ).…”

“…Such advanced analyses of the terahertz data is implemented using models from effective medium theory. The anisotropic Bruggeman model (AB-EMA) is the most commonly used approach and this method has been demonstrated to allow for the extraction of pore shape information in addition to the tablet porosity ( Bawuah et al, 2020 ).…”

Wave Propagation in an Optimized Tunable Multi-channel Flter based on One-dimensional Nano Superconductor Photonic Crystal

“…In 2004, Technology Review's editors selected THz technology as one of "10 emerging technologies that will change your world" [3]. THz technology is used in the following fields: medicine [4,5], biology [6], security [7], non-destructive evaluation [8], agriculture [9], telecommunication [10], pharmaceutical [11], spectroscopy [12,13], cultural heritage [14], etc. The abovementioned applications show that the THz technology is an interdisciplinary technology.…”