Supercritical antisolvent precipitation (SAS) is a promising technique for the micronization of pharmaceutical compounds. Like all the manufacturing processes, SAS might induce solid-state modifications, the formation of undesired polymorphic forms or degradation products and the presence of solvent residues in the final product. In this work, the influence of SAS process parameters on nalmefene HCl powder characteristics was investigated. Ethanol was used as the liquid solvent and supercritical carbon dioxide as antisolvent. Micronization experiments were performed at pressures of 130 and 150 bar, in the temperature range 40-67 degrees C, and CO2 molar fraction was between 0.95 and 0.97. Amorphous particles and particles with different degrees of crystallinity and different sizes were obtained by varying the antisolvent molar fraction at different operating conditions. High-performance liquid chromatography and headspace gas chromatography analyses were performed to verify the purity of the micronized product and the absence of residual ethanol. The structural characteristics of micronized nalmefene HCl particles were studied by differential scanning calorimetry, X-ray powder diffraction and thermogravimetry analyses. The micronization process did not induce degradation of the compound and a product with a solvent residue less than 2 p. p. m. was obtained. The process induced the modification of nalmefene HCl from hydrated to anhydrous form; at particular conditions a solvate form was also obtained. (C) Koninklijke Brill NV, Leiden and Society of Powder Technology, Japan, 2008