Numerical study on hydrodynamic characteristics of USP apparatus 3 using CFD method

With the development of dissolution testing, the assessment of hydrodynamic characteristics of dissolution apparatus is crucial for understanding drug dissolution mechanisms. Therefore, the velocity and viscous shear stress (τ_vss) distribution during a typical period are analyzed and quantified by modeling the hydrodynamics of USP apparatus 3 using CFD method. Additionally, the effects of dip rate and mesh screen on these variables are investigated. The results demonstrate that the flow field of USP apparatus 3 exhibits apparent periodicity. During a typical period, there are Circulation A and B in the upstroke and downstroke processes, resulting in two velocity and τ_vss peaks within the cylinder. After the cylinder breaks through the free liquid surface, the mean velocity within the cylinder significantly increases due to the liquid level difference, which is similar to the trend of mean τ_vss, and the τ_vss distribution is concentrated at the screens, along the walls, and in the disordered flow region. With the increase from 5 dpm to 25 dpm, the mean τ_vss significantly rises from 0.36 to 1.26 mN/m² to 0.67–3.00 mN/m² due to the increase in the liquid velocity, which can mechanistically explain the enhanced drug dissolution at higher dip rate. At 5–15 dpm corresponding to the contraction frequencies of the human small intestine, the mean τ_vss within the cylinder is in the range of 0.5–2.1 mN/m², which approximates the shear environment in the upper small intestine indicating a degree of physiological relevance. As the screen reduces from 50-ppi to 30-ppi, the velocity and τ_vss peaks associated with potential energy increase by 42.3 % and 59.3 %, respectively. Thus, this may explain that screens with better flow efficiency, due to the decrease in ppi, lead to a significant increase in velocity and τ_vss, ultimately shortening drug dissolution time. Additionally, the effect of the dip rate on the hydrodynamic characteristics is more sensitive than the screen due to the substantial increase in momentum induced by the mechanical motion. This research not only provides a mechanistic explanation for the experimentally observed drug dissolution behaviour but also offer a theoretical foundation for optimizing operation parameters to more accurately simulate physiological conditions and enhance in vitro/in vivo correlation (IVIVC).