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

Dec 17, 2020

Skelbæk-Pedersen, Anne Linnet, Mohammed Al-Sharabi, Thomas Kvistgaard Vilhelmsen, Jukka Rantanen, and J. Axel Zeitler. “Effect of particle size and deformation behaviour on water ingress into tablets.” International Journal of Pharmaceutics 587 (2020): 119645.


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.