Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Computational Modeling

Background:

• Tablet disintegration is crucial for drug absorption, involving liquid penetration, swelling, dissolution, and break-up.
• Particle swelling dynamically alters tablet pore structure during liquid uptake, impacting disintegration.
• Understanding pore space changes is key to optimizing tablet performance.

Purpose of the Study:

• To analyze pore structure changes during tablet disintegration.
• To couple a discrete element method (DEM) model with a single-particle swelling model and experimental data.
• To validate the coupled model for microcrystalline cellulose (MCC) tablets with varying porosities and croscarmellose sodium (CCS) concentrations.

Main Methods:

• Coupled discrete element method (DEM) and single-particle swelling model.
• Experimental validation using terahertz-pulsed imaging (TPI) for liquid penetration and tablet swelling.
• Simulation of MCC tablets with porosities of 10%, 15%, 22% and CCS concentrations of 2%, 5%, 8% w/w.

Main Results:

• The coupled model accurately captured swelling behavior differences based on porosity and formulation.
• Tablets with higher CCS concentrations (8% w/w) exhibited the slowest swelling.
• Simulations indicated pore closure in both wetted and dry tablet volumes, hindering liquid access and slowing swelling.

Conclusions:

• The study provides novel insights into pore space dynamics during pharmaceutical tablet disintegration.
• Pore closure due to swelling, particularly with high CCS, significantly impacts tablet disintegration rates.
• This understanding is vital for optimizing tablet formulations and predicting drug performance.