A hydrodynamic cavitation mixer (HCM) was introduced in the supercritical fluid assisted atomization (SAA) process to improve mass transfer. SAA-HCM resulted in a more homogenous primary droplet and, as a consequence, narrower particle size distributions. Levofloxacin hydrochloride (LH) being selected as a model drug, the effects of cavitation generator on morphology, size, and distribution of precipitated particles were evaluated. In addition, the influences of several process parameters, such as the feed ratio between CO2 and liquid solution, solute concentration, etc., were investigated in detail. Spherical amorphous micron-sized particles were obtained at different CO2-solution feed ratio and solute concentrations. In all cases, particles with diameters smaller than 2.1 mu m were produced. The SAA-HCM is expected to be a promising technique for producing microparticles suitable for pulmonary delivery in drug delivery applications. (C) 2007 Elsevier B.V. All rights reserved.