Terahertz time-domain spectroscopy for the investigation of tablets prepared from roller compacted granules

Roller compaction before tableting is a common unit operation to increase the processability of powders. Terahertz time-domain spectroscopy (THz-TDS) has recently been introduced as a potential process analytical technology (PAT) for measuring tablet porosity based on the refractive index of the tablet. Tablet porosity is a governing parameter for tablet disintegration and dissolution. The first aim of this study was to investigate tablets prepared from roller-compacted materials with THz-TDS to explore its usefulness for particle size evaluation of granules in tablets. Secondly, the impact of roller compaction and granule size before tablet compression on the established THz-TDS based measurement of tablet porosity was investigated. Microcrystalline cellulose and α-lactose monohydrate were roller compacted separately at five specific compaction forces (2, 4, 8, 12, and 16 kN cm^-1) and fractionated into three size fractions. Tablets were prepared from the fractionated and unfractionated granules at twelve tableting pressures and subjected to THz-TDS transmission measurements. It was possible to use the scattering behaviour of the tablets at terahertz frequencies to describe the granulated materials' particle size changes during tableting. At the same time, prediction of porosity was impaired due to the deviation of the refractive index in strongly scattering samples. A correction method was introduced in which the porosity error was corrected based on the tablet's scattering behaviour, resulting in an improved prediction of tablet porosity. In conclusion, THz-TDS is considered a promising technique for the process monitoring of tableting based on its sensitivity to porosity and particle size changes within the tablet non-destructively, with a possible application as part of an in-process control strategy of the tableting of granulated or non-granulated materials.