Data supporting the manuscript 'Effect of particle size and deformation behaviour on water ingress into tablets'

Raw data for Figures 1, 3-8 in 'Effect of particle size and deformation behaviour on water ingress into tablets' (International Journal of Pharmaceutics, volume 587, 2020)

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 µm up to the range of 355-500 µm 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 = AνB). 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

Effect of particle size and deformation behaviour on water ingress into tablets.

Drug release performance of tablets is often highly dependent on disintegration, and water ingress is typically the rate-limiting step of the disintegration process. Water ingress into tablets is known to be highly influenced by the microstructure of the tablet, particularly tablet porosity. Initial particle size distribution of the formulation and the predominant powder deformation behaviour during compression are expected to impact such microstructure, making both factors important to investigate in relation to water ingress into tablets. Two size fractions (<125 and 355-500 µm) of plastically deforming microcrystalline cellulose (MCC) and fragmenting di-calcium phosphate (DCP) were compressed into tablets with porosities ranging from 5 to 30% (with 5% increments). The total porosity of the tablets was measured using terahertz time-domain spectroscopy and liquid transport into these tablets was quantified using a flow cell coupled to terahertz pulsed imaging. It was found that tablets compressed from large MCC particles resulted in slower water ingress compared to tablets prepared from small MCC particles. In contrast, no difference in liquid transport kinetics was observed for tablets prepared across both size fractions of DCP particles. These results highlight the complex interplay between material characteristics, the process induced microstructure, and the liquid transport process that ultimately determines the drug release performance of the tablets