Coning phenomena under laminar flow.

The purpose of the present study was to investigate coning phenomena in the paddle dissolution test under laminar flow (Reynolds number <500). The minimum rotation speed at which the coning phenomena disappear (no coning rpm, NCrpm) was measured in viscous media (23 to 147mPa∙s) using various particles. The exponent values of particle size, density, and viscosity parameters in the Zwietering equation were found to be 0.066, 0.38, and 0.22, respectively. NCrpm was appropriately predicted by the Zwietering equation (average error: 8rpm). These values are very different from those for turbulent flow, suggesting that the main physical forces governing the motion of particles can be different between turbulent flow and laminar flow. This point should be taken into account when understanding the dissolution of drug products in viscous fluids representing the fed state.

Prediction of coning phenomena for irregular particles in paddle dissolution test.

The purpose of the present study was to investigate the applicability of the Zwietering equation to predict the occurrence of coning phenomena for non-spherical, porous, and swell-able particles in the paddle dissolution test. For non-spherical particles, the minimum rotation speed at which the coning phenomena disappear (no coning rpm, NCrpm) was appropriately predicted by using the Stokes diameter or the short side length of the particles. For porous and swell-able particles, NCrpm was appropriately predicted by using the Stokes density of the particles. The accuracy of the Zwietering equation was sufficient to be used for development of a dissolution test method.

Minimum rotation speed to prevent coning phenomena in compendium paddle dissolution apparatus.

The purpose of the present study was to investigate the applicability of the Zwietering equation to coning phenomena which often occur during dissolution testing. The minimum rotation speed at which coning phenomena disappeared (no coning rpm, NCrpm) was experimentally determined for various particle and fluid properties in a compendium paddle apparatus with a round-bottom unbaffled vessel. The particle size, relative density and kinematic viscosity exponents in the Zwietering equation were optimized for NCrpm. The particle size and relative density exponents were found to be similar with those for the general tank configurations of cylindrical flat-bottom baffled vessels. However, the kinematic viscosity exponent was significantly different. The equation obtained in this study showed sufficient accuracy (r(2)=0.98, average error=12rpm) to estimate the occurrence of coning. The Zwietering equation was found to be applicable to the coning phenomena in the compendium paddle apparatus.