The aim of this study was the investigation of powder-based formulations for nasal administration of tacrine hydrochloride. The anti-Alzheimer drug was encapsulated in mucoadhesive microparticles based on chitosan/pectin polyelectrolyte complexes. Microparticles were prepared by means of two different technological approaches (direct spray-drying and spray-drying followed by lyophilization) and analysed in terms of size, morphology and physico-chemical characteristics. Moreover, water uptake and mucoadhesion ability were evaluated as well as drug release and permeation behaviour. The results suggest that lyophilization favours the formation of small particle aggregates with a size of 10 μm, instead of single particles (size smaller than 5 μm) such as direct spray-drying. Particles obtained with the two loading methods present different functional properties according to the different physical state of the loaded drug and its possible interaction with chitosan/pectin complex. Moreover, the presence of different amount of chitosan and pectin in the complex influences their ability to hydrate, interact with mucin and favour drug permeation.