Design and characterization of a laminar flow-through dissolution apparatus: Comparison of hydrodynamic conditions to those of common dissolution techniques.

ABSTRACT

A flow-through dissolution apparatus was designed and evaluated to screen small quantities of pharmaceutical drug compounds early in development. The apparatus was designed to mount on a microscope slide such that a compacted solid drug was positioned flush along one wall and the fluid flow in the apparatus was laminar flow in a rectangular duct. Stereomicroscopic digital images and Raman spectra of the solid were taken during dissolution and the effluent dissolution medium was collected in fractions to determine the dissolution rate by fluorescence or HPLC/UV. Three compounds, triamterene, ketoprofen, and ß-naphthoic acid were investigated in the dissolution flow cell at various hydrodynamic conditions. In conditions where no solvent-mediated conversion was expected, there was a decrease in dissolution rate with time in the flow through cell that was associated with surface smoothing. This phenomenon also occurred in rotating disk experiments. In either case, the magnitude and time course of the decrease in dissolution rate with time is generally different enough to distinguish from the decrease in dissolution rate due to solvent-mediated conversion.