The aim of this investigation was to examine the effect of a jet-mill and spray-drying process on the physicochemical and aerodynamic dispersion properties of amiloride HCl particles. Micro-fine particles were prepared by a spiral air jet-mill Hosokawa 50 AS and Mini Spray-Dryer B-191. A 2(3-1) fractional factorial experimental design was implemented to screen three jet-mill process parameters. Possible changes in the physicochemical properties of the material due to spiral jet-milling were examined by the determination of the particle size distribution (PSI)), powder true density, powder flowability, diffuse reflectance Fourier transform infrared spectroscopy (DRIFTS) and scanning electron microscopy (SEM). The effect of different jet-milling parameters and the spray-drying process on the aerosol dispersion characteristics was examined with a cascade impactor with a preseparator using the Aerolizer (R) dry powder inhaler device (Novartis, Switzerland). The results show that small changes in the particle size within the 1 to 5 mu m range had an impact on the physicochemical and aerosol dispersion properties of jet-milled and spray-dried particles. (C) 2014 Elsevier B.V. All rights reserved.