In this study, recrystallization of adefovir dipivoxil particles was carried out by the rapid expansion of supercritical solutions (RESS) process. Supercritical carbon dioxide, which is a green solvent, was selected as a solvent. The effect of process parameters such as extraction temperature and pressure, pre-expansion temperature, spray distance, and nozzle configuration on the particle size of adefovir dipivoxil was evaluated and it was found that the process parameters did influence the particles size. The solubility of adefovir dipivoxil in CO2 was measured for the purpose of setting proper experimental conditions. Increasing the extraction temperature (308.15-328.15 K) caused the particle size of adefovir dipivoxil to increase. Particle size decreased with increasing extraction pressure (20-30 MPa). The particle size of adefovir dipivoxil increased with increasing pre-expansion temperature. An increase in the spray distance (8, 16, 32 cm) resulted in a decrease in the average size of particles. The effect of the internal nozzle diameter on the size and shape of the precipitated particles was examined using different nozzle internal diameters (152, 500, 762 mu m). When the internal nozzle diameter size was larger, the particle size did not show significant change. The adefovir dipivoxil particles that underwent RESS process were analyzed by SEM, XRD, DSC and FT-IR spectra. (C) 2013 Elsevier B.V. All rights reserved.