Uncertainties in drug dissolution tests - identification and CFD evaluation of factors limiting the accuracy of the USP2 test.

Accurate USP2 paddle dissolution testing is crucial for the quality characterisation, development, and research of solid‑dosage forms, but measurement uncertainties, particularly during the initial flow‑build‑up phase, can mask batch‑to‑batch differences. This work focuses on Computational Fluid Dynamics (CFD) using high-resolution simulations to identify and quantify the main factors contributing to uncertainty in the dissolution of single-component paracetamol tablets. CFD simulations were performed using the OpenFOAM toolkit using a custom solver that simultaneously resolves Navier-Stokes flow and the convective‑diffusive transport of paracetamol. The dissolution process was modelled using the Direct Numerical Simulation and the Smagorinsky-Lilly LES formulation with Van Driest wall damping. Targeted dissolution experiments were used to validate the numerical predictions. Laboratory-prepared tablets (500 ± 1.6 mg) were tested under three configurations: (i) free floating, (ii) magnetically fixed, and (iii) fixed with the tablet bottom coated to suppress rear‑face dissolution. Tests were conducted in a USP2 apparatus at paddle speeds of 25, 50, and 75 RPM, with sampling from 0.5 min to 40 min to capture the time dynamics. The simulated concentration and integral mass fluxes matched experimental dissolution rates.