Indomethacin (IN) is a non-steroidal antiinflammatoly drug. It reduces pain and inflammation in rheumatoid arthritis but its use is associated with high incidence of undesirable gastrointestinal side effects. In addition, its low solubility in water limits its oral bioavailability. In this work, microparticles based on an IN-polylysine (PL) complex were obtained by spray drying. The system is intended to deliver the drug through the inhalatory route for both local and systemic treatments. Several formulations, varying the relative composition IN/PL-dextrin (DX) and the total solid content of the feed solutions, were tested. The process performance (yield, air outlet temperature), product properties (IN load efficiency, moisture content, crystallinity, glass transition temperature, density, morphology and particle size distribution), the IN-polylysine ionic interaction (assessed by FT-infrared spectroscopy, powder X-ray diffraction and thermal analysis), and in vitro IN release were studied. Powders exhibited high load efficiencies and low moisture contents, and remained in the amorphous state after nine months of storage. The particle systems with 50% of the polylysine amino groups neutralized by IN were the more attractive ones for pulmonary treatment, since they were easily processed using a homogeneous aqueous feed, had relatively high IN contents and high cumulative fraction of respirable particles. (C) 2015 Elsevier B.V. All rights reserved.