The relationship between microstructure and dissolution rate of three-component granules was investigated. Granules were prepared by fluid bed granulation from sucrose spheres as model excipient, sodium chloride as model active ingredient, and polyethylene glycol (PEG) as in situ melt binder. A novel method for controlling the distribution of active ingredient within the granule was developed, based on suspending its particles in the binder prior to granulation. Granule microstructure was varied by systematically changing the NaCl particle size and the active/excipient ratio in granules. The dissolution rate of granules in water was measured by conductometry. A minimum was found in the functional dependence of dissolution time on NaCl fraction in the granule, in line with earlier computer simulations. The primary particle size was found to influence dissolution time in a nonlinear way depending on the fraction of available particle surface immersed in the binder. The intrinsic binder dissolution can therefore be rate-controlling if primary particles of the active ingredient are totally coated by binder. This was confirmed by comparing the dissolution times of granules prepared with PEGs of different molecular weight.