Purpose <p>Dissolution kinetics of tablets is pivotal to therapeutic performance, quality assessment, and troubleshooting in manufacturing. We aimed to develop and validate a simulation framework to predict tablet dissolution kinetics under realistic hydrodynamic conditions, thereby supporting process development and quality control.</p> Methods <p>We modeled the dissolution of drug particles packed within a tablet by coupling the lattice Boltzmann method (LBM) for fluid flow and transport with the discrete element method (DEM) for particle mechanics in USP Apparatus II. The framework was first validated against experimental measurements of single‑particle dissolution, then scaled to bulk-particle (tablet‑level) simulations to assess model extensibility.</p> Results <p>The coupled LBM-DEM framework reproduced experimentally observed hydrodynamics and particle dynamics in a mechanically agitated dissolution device and scaled from single‑particle to tablet‑level simulations without sacrificing fidelity.</p> Conclusions <p>This physics‑based framework enables the prediction of tablet dissolution under compendial hydrodynamic conditions and provides a foundation for incorporating additional particle‑mechanical phenomena (e.g., swelling and breakage) to fully model tablet disintegration and dissolution.</p>