Modeling of the dissolution of a pharmaceutical compound

This paper analyses the phenomena encountered in the dissolution of a powder composed by drug crystals using the complementarity between the experimental and numerical approach. A macroscopic model based on the population balance equation was developed to describe dissolution experiments. The population balance equation was discretized and solved with the method of classes. The experiments were performed in a perfectly mixed vessel. Different initial masses of solid particles were introduced. The size distribution of the initial particles was measured by image analysis to take into account the particle anisotropy. For each experiment, the evolution of the concentration during the dissolution process was followed by conductimetry. The concentration measurements show an acceleration of the overall dissolution kinetics at the beginning of the dissolution process, although the undersaturation decreases. This particular behavior suggests that the aggregated powder is first disaggregated under the effect of stirring. The introduction of a fragmentation mechanism in our model has allowed a correct description of the concentration profiles. Intrinsic dissolution kinetics was found to be controlled by mass transfer.