Abstract Fine spherical granules of uniform particle size less than 500 μm are desired for easy handling in dispensing pharmacy. These fine particles have been produced by layering an active ingredient and excipients on a core; however, several technical problems have been difficult to overcome, e.g., the amount of layered ingredients is limited and often granules themselves agglomerate during the layering process and affect the quality of the finished product. Here, we studied the feasibility of the manufacture of fine spherical granules by an extrusion/spheronization method. A screen with a pore size of 0.4 mm or smaller was used for extrusion, and reduction of the extrusion pressure at the screen was necessary to prevent the screen from breaking. In light of the reduction of the screen pressure, we found low substituted hydroxypropylcellulose (L-HPC), croscarmellose sodium (Ac-Di-Sol) and carmellose calcium (ECG ®-505), markedly decreased the screen pressure. It is suggested that the high swelling property of these excipients is closely related to screen pressure reduction. In the spheronization process, it was found that L-HPC gave the highest sphericity, while Ac-Di-Sol and ECG-505 were unsatisfactory. It is concluded that L-HPC is the most appropriate excipient for the manufacture of fine spherical granules of less than 500 μm diameter by the extrusion/spheronization method.