Multiscale modeling of aspirin dissolution: From molecular resolution to experimental scales of time and size

This paper presents a multiscale modeling approach for the dissolution of aspirin. Recent advances in multiscale simulation techniques are reviewed, and the need to derive absolute rate constants in order to predict dynamic properties during crystal growth or dissolution is highlighted. Absolute face-specific rate constants obtained in our recent study on molecular dynamics and kinetic Monte Carlo simulations are incorporated in a simulation based on the equations of classical mass transfer. As experimental reference, a Jamin-type interferometer is used to monitor the face displacement velocity and concentration gradient within the bulk liquid. An experimental setup that is consistent with the simulation settings to monitor crystal dissolution, based on a non-saturated resultant solution, is chosen. The face displacement velocity of the investigated (001) face as well as the final average concentration of aspirin in water are found to be in good agreement with the experimental data. The dissolution mechanism of aspirin is found to be diffusion-controlled in both the simulation and experiment. Furthermore, a method to predict all experimental and literature values used in the study, such as diffusion coefficients and solubilities, is presented.