The present research work is focussed on the formulation and evaluation of ofloxacin alginate microspheres for lung infection in the form of dry powder inhaler. Microspheres containing ofloxacin with a mean diameter of 2- 5 um were prepared by the spray drying of ofloxacin alginate micreosphers. The fine particle fraction (FPF) from Ofloxacin measured by a twin-stage impinger was unexpectedly found to be zero, although scanning electron microscopy showed that the drug coated the entire microsphere. coating the microspheres with sodium alginate (1%–2%) significantly increased (p < 0.05, n = 5) the FPF of SS (11.4%–15.4%), whereas coating with β Cyclodextrin had a similar effect (FPF = 11.3 ± 1.1%), The force of adhesion (by atomic force microscopy) between the Ofloxacin microspheres was reduced from 301.4 ± 21.7 nN to 110.9 ± 30.5 nN and The presence of sodium alginate and β Cyclodextrin on the Ofloxacin microspheres (detected by Scaning electron spectroscopy) affected the detachment of due to strong adhesion between the two, presumably due to capillary forces acting between them. Precoating the microspheres with excipients increased the FPF significantly by reducing the drug–carrier adhesion. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.