Spray-dried granules were observed by a laser microscopy with the immersion liquid technique. The binder distribution in the granules was analyzed from light intensity profiles of the images. The results showed that a surface layer with a large amount of the binder is formed in the spray-dried granule, and the segregation is influenced by initial binder concentration and size of atomized droplet. A computer simulation for soluble binder segregation during spray drying was conducted by considering simultaneously the solvent evaporation, the relative migration between the liquid and the particles, the diffusion, and drying shrinkage. The simulation coincides with the experimental results. To make uniform granules, reducing the amount of binder, liquid content, size of atomized droplet, and drying rate is favorable.