In this study, microspheres of trimethoprime (TMP), which is an antibiotic drug, were synthesized in a single step. To synthesize microspheres in various sizes, the amount of TMP was kept constant while mole number of the phosphazene used as crosslinker was reduced. TMP microspheres were synthesized through the precipitation polymerization technique with different mole ratios of crosslinker (1:1, 1:2, 1:3, and 1:6) and characterized by FT-IR, TG, XPS, particle size analysis and SEM-EDX analyses. An in vitro biodegradation test conducted on TMP microspheres in acidic media showed that they degraded at a ratio of 92% in 50 days. In addition, TMP microspheres were used in controlled release of Vitamin B12 and Rhodamine 6G, which had been chosen as model drugs. (C) 2014 Elsevier B.V. All rights reserved.