Impact of Density Gradients on Flow-Through Dissolution in a Cylindrical Flow Cell

Abstract

Measuring release rates for sparingly soluble compounds requires slow flow rates to achieve measurable eluent levels. However, flow rate cannot be reduced indefinitely because density gradients could measurably alter the drug release rate. Finite element simulations of convective diffusion/dissolution with an applied concentration-dependent density gradient reproduced the trends of the changes in dissolution rate on eluent flow rate which occur upon switching flow direction and sample cell orientation relative to gravitational field as observed in the literature[] employing a rectangular flow cell. The situation was experimentally reproduced using an implant obstruction placed centrally in a cylindrical flow cell.

Keywords:

• dissolution
• drug release
• flow-through release
• density gradient
• flow cell orientation
• high pressure liquid chromatography (HPLC)
• flow-rate
• solubility