A computer model was developed with the objective of modelling pharmaceutical tablet dissolution with non-swelling excipients. The model, which allows the explicit description of the tablets heterogeneous microstructure, was verified using Fourier Transform Infrared (FTIR) spectroscopic imaging and UV-visible spectroscopy. Two parametric studies were conducted using the model for binary tablets. One investigated the effect of particle size and tablet composition on component release times and the other studied the effect of changing the diffusivity and solubility of one component on the release times of both. Tablets containing Polyethylene Glycol (PEG) 4000 and nicotinamide were used in the experiments. Physical properties of pure components were obtained from literature and also experiments using tablets containing 100% and 10% (w/w) nicotinamide. The model was then used to predict the dissolution of a tablet containing 40% (w/w) nicotinamide which matched the experiment with a mean squared error of 0.08%. (c) 2010 Elsevier Ltd. All rights reserved.