Simvastatin is a drug which is widely used in the treatment of hypercholesterolemia, but it is practically insoluble in water and is not well absorbed via gastrointestinal tract. Therefore, introducing effective methods to improve its dissolution rate that may result in increased bioavailability is very important. Particle size reduction is one of the physical methods which are used to improve the dissolution rate of drugs in aqueous media. Amongst the several methods which have been used for particle size reduction, the use of supercritical fluid technology has some special advantages. In this study, the simvastatin nanoparticles (47 nm), were formed using supercritical trifluoromethane and showed a significant improvement in terms of dissolution rate. The effects of extraction temperature and pressure and spray distance on particle size were analyzed. Characterization tests included X-ray diffraction (XRD), Fourier Transform Infrared Analysis (FTIR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS). Response surface methodology (RSM) was used for experimental design and process optimization and it was found that the best results can be obtained at 10 MPa, 50 degrees C, and 7 cm. (C) 2015 Elsevier B.V. All rights reserved.