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

Terahertz time-domain spectroscopy (THz-TDS) is a novel technique which has been applied for pore structure analysis and porosity measurements. For this mainly the anisotropic Bruggeman (AB-EMA) model is applied to correlate the effective refractive index (n_eff) of a tablet and the porosity as well as to evaluate the pore shape based on the depolarisation factor L.

This paper investigates possible error sources of the AB-EMA for THz-TDS based tablet analysis. The effect of absorption and tablet anisotropy – changes of pore shape with porosity and density distribution – have been investigated. The results suggest that high tablet absorption has a negligible effect on the accuracy of the AB-EMA. In regards of tablet anisotropy the accuracy of the porosity determination is not impaired significantly.

However, density distribution and variations in the pore shape with porosity resulted in an unreliable extraction of the tablet pore shape. As an extension of the AB-EMA a new concept was introduced to convert the model into bounds for L. This new approach was found useful to investigate tablet pore shape but also the applicability of the AB-EMA for an unknown set of data.

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Materials: Microcrystalline cellulose (MCC, Avicel PH-102, FMC Europe NV, Brussels, Belgium), lactose α-monohydrate (Tablettose 100, Meggle Group, Wasserburg, Germany) and starch (Startab, Colorcon Limited, Dartfort, UK) were used as received.

An immediate release formulation of ibuprofen (BLD Pharmatech, Shanghai, China) was made with dose strength of 10% w/w. The formulation was composed of common excipients, MCC, lactose anhydrous (Supertab21AN, DFE pharma, Goch, Germany), croscarmellose sodium (CCS, DuPont Nutrition, Wilmington DE, USA) and magnesium stearate (Fisher Scientific, Fair Lawn NJ, USA).

Article information: Moritz Anuschek, Prince Bawuah, J. Axel Zeitler. Terahertz time-domain spectroscopy for powder compact porosity and pore shape measurements: An error analysis of the anisotropic bruggeman model, International Journal of Pharmaceutics: X, 2021. https://doi.org/10.1016/j.ijpx.2021.100079.