Box-Benhken design was applied to engineer spray dried mannitol particles. Particles were characterized by optical microscopy to determine size, size distribution, shape and morphology comparing to a reference material commercially available. Two shape factors calculated with the results of image analysis, circularity and projected area equivalent diameter (Heywood diameter), as well as span value for size distribution, were chosen as responses for analyses of variance. Outlet temperature was shown to be the most important factor to control during the process in order to produce particles with high value of circularity. Particle size represented as Heywood diameter was affected by ethanol while particle size distribution was affected by concentration of mannitol solution. Desirability function was applied to determine the best process parameters and to predict the responses, which were confirmed experimentally. Morphology was evaluated with scanning electron microscopy and confirmed results of ANOVA for circularity, showing that regulars and spherical particles were produced at low temperature. FTIR and DRX were used to demonstrate that particles did not modify polymorph after the spray drying keeping the same beta-form of the raw mannitol. (C) 2015 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.