Assessing dissolution kinetics of powders by a single particle approach

A novel methodology for studying the dissolution of powders based on a "single particle" approach is presented. A single particle is the basic unit composing the bulk of a powder, and vast information could be gained from its dissolution kinetics. The dissolution of a single particle was measured by means of a microscopy-based experimental method with custom-developed image analysis algorithms. The effects of various liquids and their physical properties on the dissolution kinetics were studied. A mathematical model based on a shrinking sphere was utilized to describe the dissolution process. The rate constant was derived from the experimental data for each tested condition and correlated with the viscosity of the dissolving medium. A significant effect, mostly at low viscosity values was found. The derived values are in accordance with the diffusive behavior as predicted from the Einstein-Stokes equation. Isothermal calorimetry was used to measure the enthalpy of dissolution, and correlated with the rate constant derived from the single particle dissolution measurements. Faster dissolution rate corresponded with the lowest endothermic dissolution enthalpy. Consequently, it is proposed that the dissolution of particles is not simply a mass transfer limited process and it also includes heat transfer related mechanism(s) that should be further studied.