In this paper, the ultrafine ciprofloxacin (CPF) particles were prepared by the reactive precipitation of ciprofloxacin hydrochloride (CPF center dot HCI) and NaOH aqueous solution with the presence of isopropyl alcohol (IPA) as the anti-solvent. Subsequently, microsized spherical CPF aggregates were generated using the prepared ultrafine particles as building blocks by spray drying method. The effect of the volume ratio of the CPF solution to anti-solvent (IPA) was investigated. The result shows that the ultra-fined particles of ciprofloxacin can be produced under the volume ratio of 1:15. After spray drying, 3-4 mu m spherical aggregates with ultrafine primary CPF particles can be obtained and exhibited great improved aerosol performance with fine particle fraction (FPF) up to 60%. (C) 2009 Elsevier B.V. All rights reserved.