Non-destructive quantification of fragmentation within tablets after compression from scattering analysis of terahertz transmission measurements

Material deformation behaviour has a critical impact on tablet formation. Fragmentation is one of the key mechanisms affecting the strength of a final compact, however, quantitative methods for estimating fragmentation are often complex, destructive and time-consuming. The purpose of this study was to investigate the applicability of terahertz time-domain spectroscopy (THz-TDS) to quantify fragmentation upon tableting. Up to five size fractions of microcrystalline cellulose (MCC), dibasic calcium phosphate (DCP), and lactose monohydrate (lactose) in the range of < 125 mu m up to the range of 355-500 mu m were compressed into tablets and analysed with THz-TDS. The effective refractive index and absorbance spectra of whole tablets were measured in transmission, and the optical properties were clearly affected by fragmentation upon compression. The scattering observed from the absorbance spectra was fitted into a power law equation (y = A nu(E)). It was observed that up to pressures of 50 MPa the values of parameter A that were extracted from the power law fit decreased exponentially with increasing compression pressure. For higher compression pressures the value of A remained constant. This observation was more pronounced for DCP, followed by lactose and then MCC and the effect was more pronounced for larger compared to smaller initial particles. The non-destructive measurements correlated with previously obtained results based on particle size distribution measurements of the particles before compression and those obtained from destructive analysis of tablets. The terahertz method can resolve similar differences in fragmentation behaviour upon compression compared to the particle size analysis but requires no sample preparation.