2025 AIChE Annual Meeting

(221f) Bridging Micro-Scale Compression Behavior with Macro-Scale Failure Analysis in Pharmaceutical Tablets

Authors

Predictive first-principles physics models are critical for understanding tablet failure mechanisms, such as fracture, delamination, and capping, which directly impact drug dosage accuracy and patient safety. Current finite element analysis (FEA) approaches face three key limitations: (1) reliance on empirical material parameters that lack microstructural granularity, (2) computational constraints in modeling complex powder interactions during compaction, and (3) difficulty capturing stress concentration effects at critical interfaces like score lines and particle boundaries. While FEA effectively simulates continuum-level stresses, its predictive capability diminishes when handling large plastic deformations and adhesive interactions inherent to pharmaceutical powders. These challenges necessitate improved modeling frameworks that bridge micro-scale particle behavior with macro-scale tablet integrity.

This work introduces an approach in Discrete Element Model (DEM) incorporating elasto-plastic, plastic, and cohesive/adhesive interactions to simulate high-density powder compaction. By explicitly modeling each particle as a deformable finite element and capturing the interparticle (and element) forces through a variational formulation, the framework captures both elastic recovery and permanent deformation at large strains – a regime where conventional DEM fails. The DEM outputs provide critical input parameters for a discrete particle continuum (DPC) model that could enhance FEA predictions of tablet failure modes. This hybrid DEM-FEA framework enables first-principles prediction of critical quality attributes like tensile strength and friability during formulation design.