Roxithromycin (ROX), a class W drug has 50% absolute oral bioavailability due to poor aqueous solubility. The present study deals with exploring the effect of homogenization, homogenization followed by freeze drying and homogenization followed by spray drying in the presence of solubilizers on drug solubility and dissolution rate. Homogenization and subsequent freeze drying resulted in 3-4 fold increase in saturation solubility and 18 times faster dissolution as compared to the pure drug. In this study, a more preferred aqueous system was developed for enhancement of the saturation solubility and dissolution rate and compared with the non-aqueous system. Interestingly the aqueous system was found equally effective and comparatively more stable. Enhancement of the saturation solubility and dissolution rate was a result of significant particle size reduction, improved hydrophilicity and complete or partial transformation to amorphous form as evidenced by DSC and XRPD studies. The study focused on utilization of solubilizer to synergistically enhance the efficiency of the processing techniques. The effect of processing and formulation variables on the saturation solubility, in vitro dissolution, drug crystallinity, physical interaction, antimicrobial activity and stability was also monitored. (c) 2006 Elsevier B.V. All rights reserved.