Supercritical fluid-assisted atomization has been used to micronize erythromycin in the range of aerosilizable drugs. This process allows a very efficient production of micro-particles due to the release of supercritical CO2 from the inside of the primary droplets formed during the atomization process. The experiments have been performed using three different organic solvents (methanol, ethanol, acetone) and the influence of several process parameters: feed ratio between CO2 and liquid solution, concentration of solute in the liquid solution and precipitation temperature, have been tested. Spherical micrometric and non-coalescing particles have been obtained using methanol and ethanol at various CO2-solution feed ratio and concentrations. In all cases, particles with diameters smaller than 3 mum have been obtained; up to 88% of the particles volume was included in the range from 1 to 3 mum, at the most favourable operating conditions. In the case of acetone, well-defined spherical particles were obtained only when a feed ratio of 1.6 was used, in all the other experiments the particles coalesced in large groups. No degradation occurred to erythromycin as shown by the comparison of the HPLC traces of processed and raw materials. Head space GC analysis revealed a maximum solvent residue in the processed material of 90 ppb. (C) 2004 Elsevier B,V. All rights reserved.