For the treatment of osteomyelitis and the prevention of infections after orthopedic surgery, topically implantable gentamicin sulfate (GS)-loaded poly (D, L-lactide-co-glycolide) microparticles (GSMP) containing glycolide monomer (GM), as a biodegradable and nontoxic material, were prepared by melt-extrusion method without organic solvent for controlled release. After preparation of polymer blend, the powders of different size (90-1200 mu m) were obtained by means of freezer-mill. The influences of GM and particle size were investigated on the GS release patterns. GSMP containing GM (in case of 10% loaded) showed a near-zero order release from 2 to 7 days with the initial burst. GM affected to increase of GS release rate during the in vitro release test. The pH variations of the media were investigated to determine effect of GM on pH drop of media. The morphological evaluations, change of molecular weight, and thermal property of microparticles were characterized by scanning electron microscope, gel permeation chromatography, and differential scanning calorimeter, respectively. Bacterial inhibition zone test was established to identify antibiosis of GS. It showed antibiotic areas except control sample. From these results, the authors expected that GSMP containing GM would be a good dosage form as a topically implantable device that can get rid of lag period of GSMP. (c) 2007 Wiley Periodicals, Inc.