Comparative Evaluation of Dissolution Performance in a USP 2 Setup and Alternative Stirrers and Vessel Designs: A Systematic Computational Investigation

The dissolution testing method described in the United States Pharmacopeia (USP) Chapter ⟨711⟩ is widely used for assessing the release of active pharmaceutical ingredients from solid dosage forms. However, extensive use over the years has revealed certain issues, including high experimental intervariability observed in specific formulations and the settling of particles in the dead zone of the vessel. To address these concerns and gain a comprehensive understanding of the hydrodynamic conditions within the USP 2 apparatus, computational fluid dynamic simulations have been employed in this study. The base design employed in this study is the 900 mL USP 2 vessel along with a paddle stirrer at a 50 rpm rotational speed. Additionally, alternative stirrer designs, including the hydrofoil, pitched blade, and Rushton impeller, are investigated. A comparison is also made between a flat-bottom tank and the USP round-bottom vessel of the same volume and diameter. Furthermore, this work examines the impact of various parameters, such as clearance distance (distance between the bottom of the impeller and bottom of the vessel), number of impeller blades, impeller diameter, and impeller attachment angle. The volume-average shear rate (