Indomethacin (IMC) nanoparticles were formed by cogrinding with dextrin under defined moisture conditions. We investigated the mechanism by which IMC nanoparticles are formed and the factors affecting their formation. Cogrinding of IMC and dextrin with optimal water content yielded more than 60% nanoparticles with an average size of 100-200 nm in aqueous solution. Mixtures ground in dry or higher moisture conditions yielded a lower proportion of IMC nanoparticles. The water content producing maximum yields of nanoparticles varied depending on the weight ratio of dextrin to IMC, and the molecular weight of dextrin. Powder X-ray diffraction and solid-state NMR measurements demonstrated that the molecular state of IMC in ground mixture (GM) of IMC and dextrin at suitable moisture condition was mostly crystalline, while that of GM at dry condition was a mixture of amorphous and crystalline forms. The morphology of nanoparticles observed by atomic force microscopy in aqueous solution was soft at the outer surface, suggesting dextrin may adsorb on the IMC nanocrystal surface. Water during grinding could facilitate the dispersion of nanocrystalline IMC into the dextrin matrix. The effective adsorption and interaction of dextrin on the IMC nanocrystal surface could inhibit the aggregation after dispersing in water. (c) 2012 Elsevier B.V. All rights reserved.