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.
Highlights
Terahertz technology has attracted considerable interest for a range of application scenarios
Markl el al. [44] showed that the assumption of the spherical inclusion in the Bruggeman effective medium approximation can limit the accurate prediction of the effective refractive index when tablets containing active pharmaceutical ingredients (APIs) and those composed of a highly porous excipient, such as functionalised calcium carbonate, are tested. This led to the adoption of the anisotropic Bruggeman effective medium approximation (AB-EMA), which takes into consideration the presence of non-spherical inclusions within a tablet
The knowledge of the g factor permits the prediction of the pore shape, which is an added merit of the AB-EMA compared with both the zero-porosity approximation (ZPA) and TBEMA methods. This terahertz porosity measurement method always demands the use of a flat-faced tablets set with known nominal porosities and effective refractive index values determined in TD or in FD
Summary
Terahertz technology has attracted considerable interest for a range of application scenarios. The upper bound indicates an ideal parallel arrangement of the solid material and air voids with respect to direction of the THz electric field whereas the lower bound represents an ideal serial arrangement [39] These two studies triggered a number of completely new ways of assessing the quality of pharmaceutical tablet using THz-TDS. [44] showed that the assumption of the spherical inclusion in the Bruggeman effective medium approximation ( onwards known as the traditional Bruggeman effective medium approximation, TB-EMA) can limit the accurate prediction of the effective refractive index when tablets containing API and those composed of a highly porous excipient, such as functionalised calcium carbonate, are tested This led to the adoption of the anisotropic Bruggeman effective medium approximation (AB-EMA), which takes into consideration the presence of non-spherical inclusions within a tablet. The use of flat-faced tablets, aside from being simple and easy to compact, will ensure accurate material parameter estimation of the intrinsic refractive index of the solid matrix
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