In this work nano-hydroxyapatite/chitosan (n-HAp/CS) hybrid microparticles were prepared by spray drying following a methodology where, in a first step, aqueous nanodispersions of n-HAp in the presence of chitosan were produced by fast stirring at pH values below and above chitosan pKa (5.5 and 7.0, respectively). The mixing system used allowed the production of homogeneous and stable nanodispersions, and the subsequent spray-dried microparticles, incorporating highly pure HAp nanoparticles of approximately 50 nm, were successfully produced without degrading the organic component, chitosan. Comparatively with the n-HAp/CS-7.0, the n-HAp/CS-5.5 dispersions were characterized by a lower particle size and a higher zeta potential, being then more stable. Differences in the spray-dried microparticles were also evident from a morphological point of view. HApCS-5.5 microparticles, which present an average size in volume of 15.8 mu m and n-HAp crystals homogenously distributed, were found to be preferred over the HApCS-7.0 counterparts, which require an extra step in the productive process and presented a tendency to form large agglomerates. Both prepared hybrid particles presented similar composition to that one of natural bone (HAp/CS of 70/30) and no traces of KCl salts were observed if a washed n-HAp paste was used. (C) 2016 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.