In pharmaceutical industry, many drugs exhibit poor solubility in biological fluid. Solubility of drugs affects on the rate of dissolution and bioavailability in biological fluids. The bioavailability of drugs can be enhanced by decreasing the drug particle size. In this study, sulindac was micronized via rapid expansion of supercritical solution (RESS) where CO2 was used as a solvent. The experiments were conducted to investigate the effect of the extraction pressure and temperature (140-230 bar and 40-60 degrees C), collection distance (1-10 cm), effective nozzle diameter (450-1700 mu m) and nozzle length (2-15 mm) on the size and morphology of the sulindac particles. The size and morphology of the precipitated particles were monitored by scanning electron microscopy (SEM). The particle size of intact sulindac particles was about 33.03 mu m, while the average particle size of the micronized sulindac particles was between 0.76 and 8.02 mu m based on different experimental conditions. Additionally, the different morphology of the micronized particles was observed like needle, rectangular, quasi spherical and irregular form while the morphology of the intact particles of sulindac was rectangular and irregular. (C) 2010 Elsevier B.V. All rights reserved.