Ibuprofen is a non-steroidal anti-inflammatory drug whose pharmaceutical activity can be improved by reducing particle size. In this study, the micronization of ibuprofen using the rapid supercritical solution expansion (RESS) process was investigated. Due to the high solubility of ibuprofen in supercritical CO2, the extraction temperature and pressure in the RESS process are considered to be little more than the critical point of SC-CO2. Unprocessed and transformed ibuprofen powders were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR). FT-IR analysis and XRD patterns of the processed ibuprofen showed that the degree of crystallinity was reduced without any chemical structural change. DSC analysis showed a 3.8 K decrease in melting point compared to that of bulk ibuprofen. Furthermore, RESS treatment of ibuprofen leads to spherical particles in the range of 50 to 200 nmas reflected by SEM observations. Keywords: rapid supercritical fluid expansion, ibuprofen, drug delivery, crystallinity, micronization. Introduction 40% of new drugs developed in the pharmaceutical industry are lipophilic and, due to their poor solubility in water, fail to reach the market [1]. Some of them are: ibuprofen, carbamazepine, miconazole and paracetamol. Therefore, there is always an urgent need to improve the dissolution rate and oral bioavailability of poorly water-soluble drugs. Various techniques are available to improve the solubility of these drugs, such as pH adjustment, microemulsification, self-emulsifying drug delivery systems, particle size reduction, and supercritical fluid (SCF) process [2]. Supercritical fluid technology is a relatively new technique for micro...... paper half ......and length based on the particle size of the product and they also compared the dissolution kinetics of raw ibuprofen and of micronized ibuprofen produced by the RESS process [22]. The results show that pre-expansion pressure and nozzle length have no effect on particle size, but an increase in spray distance results in a slight decrease in particle size. Additionally, the dissolution rate of micronized ibuprofen increases as the particle size decreases. Rapid expansion of supercritical solution was applied to particle size reduction of ibuprofen in this research, and the effect of extraction pressure and temperature was studied on particle size and morphology. Furthermore, the aim of the present study is the detailed characterization of the physicochemical properties of micronized ibuprofen particles. These include: surface properties, crystallinity, morphology, thermal behavior and chemical structure.