Drug nanoparticle formation from a ternary ground mixture consisting of a poorly water-soluble drug, hydroxypropylmethylcellulose (HPMC), and sodium dodecyl sulfate (SDS) was investigated. Flurbiprofen, which did not show nanoparticle formation by co-grinding with polyvinylpyrrolidone (PVP) and SDS, was used as a model drug. Flurbiprofen, HPMC and SDS were mixed at the weight ratio of 1:3:1 and ground for 30 min in a vibrational rod mill. The drug nanoparticle formation was observed after the ternary ground mixture (GM) was dispersed into distilled water. Molecular interactions both between flurbiprofen and HPMC and between polymer and surfactant were found to be important factors for the nanoparticle formation. The GM was stable for 2 months at the storage condition of 40 degrees C and RH 22%. Mean particle size of the dispersed particles was still less than 350 nm after storage at 25 degrees C for 1 month. It was found that the drug/HPMC/SDS ternary grinding method was applicable not only for flurbiprofen but also for other hydrophobic drugs, such as tolbutamide, probucol, phenytoin and griseofulvin. The drug nanoparticles were also obtained using other cellulose derivatives, indicating that these pharmaceutical excipients were alternative to PVP for the grinding-induced drug nanoparticle formation.