Engineering Tools for Understanding the Hydrodynamics of Dissolution Tests

Abstract

In this article, three well-established engineering tools are used to examine hydrodynamics in dissolution testing apparatuses. The application of these tools would provide detailed information about the flow, shear, and homogeneity in dissolution tests. Particle image velocimetry successfully measures two-dimensional cross-sections of the velocity field in an experimental device under both laminar and turbulent conditions. The velocity field is also calculated with computational fluid dynamics (CFD), which can rapidly provide data that is difficult or impossible to obtain experimentally. The occurrence of segregated regions within a USP Apparatus II under mild agitation conditions is revealed by CFD simulations and confirmed by laser-induced fluorescence experiments. The results clearly demonstrate that under current operation settings, the USP Apparatus II operates in a regime where the flow is in incipient turbulence, which is a highly time-dependent condition that might explain possible inconsistencies in dissolution results. It is further demonstrated that proposed changes advocating lower speeds or smaller vessels displace the system toward laminar flow conditions characterized by segregation, compromising the robustness of the test and making it vulnerable to variability with respect to sample location.

Computational fluid dynamics modeling of the paddle dissolution apparatus: Agitation rate, mixing patterns, and fluid velocities

“…Mixing appears also to be suboptimal in the regions immediately inside the vessel walls, in the upper half of the cylindrical volume of the vessel. The previous speculation on poor mixing between zones above and below the paddle 13,16 is not evidenced by the CFD simulations, as the path-lines do not predict a dead-zone of mixing between these 2 regions (at the level of the paddle).…”

“…[13][14][15] More recent studies have used computational fluid dynamics (CFD) to further elucidate the complex hydrodynamics in the test vessel. 16,17 These studies have highlighted a possible problem associated with dead zones in the vessel and potential mixing problems at low rotational speeds between the upper and lower halves of the vessel.…”

“…Only limited information on the change in hydrodynamic conditions with paddle rotational speed has been generated to date for the paddle apparatus. [14][15][16] Scholz et al 19 have recently shown that the USP paddle dissolution apparatus can be used to simulate variations in hydrodynamics in the upper gastrointestinal tract, provided that an appropriate rotational speed is used. Using both coarse and micronised felodipine powder, they concluded that the best agreement of the in vivo and the in vitro data resulted when paddle speeds of 75 rpm and 125 rpm, simulating "fasted" and "fed" state hydrodynamics in vivo respectively, were used.…”

Evaluation of Dissolution Hydrodynamics in the USP, Peak™ and Flat-Bottom Vessels Using Different Solubility Drugs

“…A variety of techniques such as ultrasound pulse echo (4), particle image velocimetry (5) and computational fluid dynamics (5,6) have been successfully utilized for the characterization of vessel hydrodynamics. These articles have reconfirmed the presence of a dead zone at the bottom of the USP vessel underneath the paddle.…”

A Comparison of USP Paddle With CrescentShaped Spindle Dissolution Profiles

“…The ability of dissolution to fulfill all of these roles is dependent on the reliability of the dissolution procedure. It has been well documented in the literature that the hydrodynamics of USP Apparatus 2 (paddle) may result in poor reproducibility and also poor variability in profiles not related to the formulation or in vivo characteristics (1,2). Attempts to fully understand and prevent poor hydrodynamics at low paddle rotation speed has allowed for the advent of new dissolution techniques such as flat-bottom vessels or Peak TM vessels (3) to reduce cone formation,and only limited comparative data has been obtained on a new paddle design,the crescent-shaped spindle.…”