Series of microparticles containing salmeterol xinafoate (SX) as active pharmaceutical ingredient (API) and lactose, mannitol or trehalose as a bulking agents were prepared using spray freeze drying (SFD) technique and the effects of sugar type and presence of hydroxy propyl beta cyclodextrin (HP beta CD) on the physical properties of powders were evaluated. Precipitation of salmeterol in the presence of lactose and mannitol resulted in the formation of irregular shapes of microparticles with broad size distributions. However application of trehalose resulted in the formation of porous particles with spherical morphology. Addition of cyclodextrin in the formulations was generally helpful for formation of porous and spherical particles with narrow size distribution with a mean size of 10-30 mu m. Dissolution of SX from processed particles was substantially higher (similar to 90% drug release in 30 min) than that of unprocessed drug and physical mixture of drug and cyclodextrin (similar to 22% drug release in 30 min). This study showed that, processing of SX by SFD technique could be a constructive approach to the production of various forms of drug and drastic changes in the physical characteristics of microparticles could be achieved by changing the composition of bulking agent and cyclodextrin. (C) 2012 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.