The main goal of this work is to investigate the physical and chemical properties of fluticasone propionate (FP), mometasone furcate (MF) and salmeterol xinafoate (SX) after being size-reduced by jet-milling OM) and wet polishing (WP) technologies. FP, MF and SX crystals were size-reduced by JM and WP until a volumetric median particle size (Dv50) of 2 pm. Additionally, FP particles were also produced by WP to target a Dv50 of 3 mu m. The micronized APIs were analyzed by laser diffraction, scanning electron microscopy, modulated differential scanning calorimetry, X-ray powder diffraction, Karl-Fischer, dynamic vapour sorption, mercury intrusion, Brunauer-Emmet-Teller adsorption method and by gas chromatography. The FP and MF powders size-reduced by IM presented a higher specific surface area (SSA), rugosity, porosity and water content and lower skeletal density, bulk density and solvents content when compared to the WP powders. On the other hand, SX by JM powders presented lower SSA, rugosity and porosity and higher densities compared to the WP powders. FP size-reduced by WP to a Dv50 of 2 and 3 mu m showed identical physicochemical properties. The JM and WP technologies produced FP, MF and SX powders with a similar PSD suitable for inhalation delivery but with distinct physicochemical properties that were technology dependent. These singular attributes may impact the interfacial properties and therefore the final drug product behavior, indicating that additional characterization of micronized API eight be recommended-for establishing-meaningful-and.performance oriented specifications. (C) 2016 Elsevier B.V. All rights reserved.