Dissolution Kinetics of a BCS Class II Active Pharmaceutical Ingredient: Diffusion-Based Model Validation and Prediction.

In this work, a diffusion-theory-based model has been devised to simulate dissolution kinetics of a poorly water-soluble drug, ibuprofen. The model was developed from the Noyes-Whitney equation in which the dissolution rate term is a function of the remaining particulate surface area and the concentration gradient across the boundary layer. Other dissolution parameters include initial particle size, diffusion coefficient, material density, and diffusion boundary layer thickness. It is useful for predicting nonsink circumstances under which pure API polydisperse powders are suspended in a well-mixing tank. The model was used to compare the accuracy of simulations using spherical (single dimensional characteristic length) and cylindrical particle (multidimensional characteristic lengths) geometries, with and without size-dependent diffusion layer thickness. Experimental data was fitted to the model to obtain the diffusion layer thickness as well as used for model validation and prediction. The CSDs of postdissolution were also predicted with this model, demonstrating good agreement between theory and experiment.