The purpose of this study was to prepare orally disintegrating tablets (ODTs) by directly compressing a mixture of sugar alcohol (mannitol) and micronized crospovidone (M-CPVP). When the mixture of mannitol and M-CPVP was co-processed by ball milling, the physicochemical properties of the resultant tablets were considerably improved, particularly their stability during storage. Several types of coground mixtures using a different ratio of M-CPVP/mannitol and processing time were tested to determine the appropriate aggregates for designing the ODTs. Without this co-processing, the powder mixture had poor compactibility, and the stability of the tablet was inferior, probably due to the high hygroscopicity of M-CPVP. The ODTs containing coground M-CPVP/mannitol showed good stability for six months under humid conditions with rapid disintegration (<30 s) and increased hardness of the tablets (tensile strength > 1.0 MPa). Tablet stability could not be achieved using a physical mixture of M-CPVP/mannitol without including the coground process. We also demonstrated that ODTs containing an active ingredient, acetaminophen, could be prepared using this cogrinding method. (C) 2013 Elsevier B.V. All rights reserved.