Hydrodynamic Complexity Induced by the Pulsing Flow Field in USP Dissolution Apparatus 4

Abstract

USP dissolution Apparatus 4 can have a pulsing or non-pulsing flow, with most commercial apparatus employing a pulsing flow. Overall, a low velocity flow field is present, particularly in the larger 22.6-mm diameter cell. Dissolution data, computational fluid dynamics (CFD), and imaging methods are used and discussed to investigate the effects of low velocity pulsing flow on dissolution. Local velocity patterns, density gradients, and the effect of flow rate on particulate dispersion can all contribute to the observed dissolution rate. In silico simulation tools and imaging techniques have proved useful in determining local hydrodynamics and, in some cases, their effect on observed dissolution rates. Methods to investigate concentration gradients at the dissolving surface are required to investigate further the effect of hydrodynamics on the dissolution process. In conclusion, it is necessary to take local flow patterns and velocities into account, rather than overall flow rate alone, when interpreting dissolution rate data in the flow-through apparatus.

A mathematical analysis of drug dissolution in the USP flow through apparatus

“…Table (6) compares a selection of predicted dissolution rates with those of experiment in the large flow through cell and a free convection system as reported by D'Arcy et al [9,10]. The predicted results exhibit some similarities to those of experiment in the sense that no significant increase in the mass transfer rate from the surface is recorded with increased volumetric flow rate.…”

“…Experiments have been conducted by D'Arcy et al [8,9,10] in the large flow through cell using non disintegrating compacts composed of benzoic acid, and with a diameter of 13mm. The experiments were conducted for different flow rates including when the pump is idle and the flow is that of pure natural convection.…”

“…For the purpose of estimating the dissolution rate from the surface, a time averaged constant upward flow is taken in place of this semi-sinusoidal profile, for the period over which the pump is active. Experimental [10]. In these experiments a compact of 8.5mm in diameter is used in the smaller flow through cell and a compact of 13mm in diameter used for the larger cell, both with an approximate height of 3mm.…”

“…This is illustrated in figure (2). Wherever available, the results are compared with those of experiment, as reported by D'Arcy et al [10].…”

“…Equation (9) is applied to the flat surface of both the large and small compacts, the results of which are shown in table (2). D'Arcy et al [10] report that for the case of natural convection the experiment is conducted using a so called Free Convection System, as illustrated in figure (3). The introduction of this additional boundary, namely the jar lid, may not be ignored.…”