The aim of the present study was to formulate and characterize diclofenac sodium (DNa)-eudragit (R) RS100 nanoparticles and solid dispersions. The conventional double-emulsion solvent diffusion technique for preparing nanoparticles of the water-soluble drugs is limited due to low encapsulation efficiency because of the drug rapid partitioning to t\he external aqueous phase. So therefore, nanoparticles of DNa with different amounts of eudragit (R) RS100 were prepared by a modified single-emulsion solvent diffusion method. The solid dispersions were also formulated using co-evaporation technique. The physicochemical characteristics of the prepared formulations were assessed operating particle size analysis, differential scanning calorimetry. X-ray crystallography, Fourier transform infrared spectroscopy and transmission electron microscopy. The release rate of DNa from the prepared nanoparticles and solid dispersions was investigated as well. The size of relatively monodisperse nanoparticles ranged from 103 nm to 170 nm. Employing the modified single-emulsion solvent diffusion technique to prepare the nanoparticles could perfectly improve the drug encapsulation efficiency. Both nanoparticles and solid dispersions of DNa-eudragit (R) RS100 displayed lower crystallinity and the intermolecular interaction between drug and polymer could not be ruled out. All the solid dispersions revealed slower drug release rate in comparison with the nanoparticles. DNa-eudragit (R) RS100 nanoparticle with the low drug/polymer ratios could relatively reduce the drug release rate up to 5 h whereas the solid dispersions were found to be suitable to control drug release for an extended times. As stated by these findings, formulation of the DNa-eudragit (R) RS100 nanoparticles was able to adjust the physicochemical characteristics of the drug and may well increase the anti-inflammatory effects of drug following its ocular or intra-joint administration. (C) 2011 Elsevier B.V. All rights reserved.