The microstructure of spray-dried model granules, comprising silica microspheres and poly(vinylalcohol), was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) with an ultramicrotome technique. Disintegration of granules was characterized by a shear method for granular beds, and by a compression test for single granules. The internal structure changed significantly with the pH of the slurry from which the granules were spray-dried. Granules from pH 7 slurry showed the smallest apparent density, and were disintegrated under the smallest applied load. By analysing the relationship between microstructure, apparent density and flow behaviour of the slurries, it was possible to obtain a guideline for preparation of appropriate granules with controlled microstructure and strength.