Modelling the evolution of pore structure during the disintegration of pharmaceutical tablets

Soundaranathan, Mithushan and Al-Sharabi, Mohammed and Sweijen, Thomas and Bawuah, Prince and Zeitler, J. Axel and Hassanizadeh, S. Majid and Pitt, Kendal and Johnston, Blair F. and Markl, Daniel (2023) Modelling the evolution of pore structure during the disintegration of pharmaceutical tablets. Pharmaceutics, 15 (2). 489. ISSN 1999-4923 (

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Pharmaceutical tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the blood stream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution and break-up. One key dependence is the dynamic change of the pore space in a tablet caused by the swelling of particles while the tablet takes up liquid. This study analyses the changes in pore structure during disintegration by coupling the discrete element method (DEM) with a single particle swelling model, and experimental liquid penetration data from terahertz pulsed imaging (TPI). The coupled model is demonstrated and validated for pure microcrystalline cellulose (MCC) tablets across three porosities (10, 15 and 22 %) and MCC with three different concentrations of croscarmellose sodium (CCS) (2, 5 and 8 %w/w). The model was validated using experimental tablet swelling from TPI. The model captures the difference in swelling behaviour of tablets with different porosities and formulations well. Both experimental and modelling results show that the swelling is slowest (i.e. time to reach the maximum normalised swelling capacity) for tablets with the highest CCS concentration, cCCS = 8%. The simulations revealed that this is caused by the closure of pores in both wetted volume and dry volume of the tablet. The closure of pores hinders the liquid from accessing other particles and slows down the overall swelling process. This study provides new insights into the changes in pore space during the disintegration, which is crucial to better understand the impact of porosity and formulations on the performance of tablets.


Soundaranathan, Mithushan, Al-Sharabi, Mohammed, Sweijen, Thomas, Bawuah, Prince, Zeitler, J. Axel, Hassanizadeh, S. Majid, Pitt, Kendal, Johnston, Blair F. ORCID logoORCID: and Markl, Daniel ORCID logoORCID:;