Investigating the effect of solubility and density gradients on local hydrodynamics and drug dissolution in the USP 4 dissolution apparatus

Abstract

Please cite this article as: D'Arcy, D.M., Liu, B., Corrigan, O.I., Investigating the effect of solubility and density gradients on local hydrodynamics and drug dissolution in the USP 4 dissolution apparatus., International Journal of Pharmaceutics (2010Pharmaceutics ( ), doi:10.1016Pharmaceutics ( /j.ijpharm.2011 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe aim of this investigation was to evaluate the effect of solubility and related solution density gradients, on hydrodynamics and dissolution rate in a low velocity pulsing flow, in the USP 4 5 flow-through dissolution apparatus. The paddle apparatus, flow-through apparatus and a free convection system were used in dissolution testing, using Benzoic Acid (BA) and Lactose Monohydrate (LM), representing slightly and freely soluble model compounds, respectively. A flow rate of 8 ml min -1 (22.6 mm diameter cell) was used in the flow-through apparatus.Computational fluid dynamics (CFD) simulations were used to analyze the effect of the dissolved 10 compounds on local hydrodynamics. A higher dissolution rate of both BA and LM was obtained in the free convection system compared to the flow-through apparatus, with highest dissolution rate from both compounds in the paddle apparatus. The effect of downward flow arising from natural convection had a significant effect for the more soluble compound, LM, on local fluid velocities, whereas flow reversal induced by the forced convection environment was a significant 15 feature impacting on the hydrodynamics in the BA species transfer simulation. The effect of solution density on local hydrodynamics needs to be considered when selecting dissolution conditions in the USP 4 dissolution apparatus.

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

“…Throughout the analysis values for the saturation concentration, C s , coefficient of diffusion, D, and the kinematic viscosity, ν, are taken to be 4.564 × 10 −3 g/cm 3 , 1.236 × 10 −5 cm 2 /s and 0.7 × 10 −2 cm 2 /s respectively. These values correspond to benzoic acid dissolving in 0.1M HCl, as reported by D'Arcy et al [8].…”

“…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.…”

“…As mentioned in section (1.3), the case for natural convection only is performed by D'Arcy et al [8,9,10] in a so called Free Convection System. In this system the compact is adhered to the lid of a jar.…”

“…Finally, it should be noted that in order to mathematically model the process of drug dissolution from the surface of a compact in the flow through cell, a constant time averaged velocity was taken as an approximation to the semi-sinusoidal velocity profile produced by the pump during experiments by D'Arcy et al [8,9,10]. This constant upward velocity may be viewed as the limiting case.…”

Characterization and Simulation of Hydrodynamics in the Paddle, Basket and Flow-Through Dissolution Testing Apparatuses - A Review

“…In addition to this noted inhibitory effect of the flow regime on dissolution at low flow rates, the solubility of the dissolving solute was observed to be a further confounding factor (54). The reduction in dissolution rate in the FTC apparatus, in comparison with the free convection system, was more marked during the dissolution of a lactose compact than a benzoic acid compact in 0.1M HCl (54).…”