The present investigation was aimed at developing a controlled release dosage form of 'ibuprofen-loaded polymethacrylate microspheres' by optimization technique using software based response surface methodology. The microspheres were prepared by emulsion solvent evaporation method in which three process variables were of importantce such as drug:polymer ratio, stirring speed and emulsifier concentration. The desired responses are percentage yield, particle size, entrapment efficiency and in vitro drug release in 12h from the microspheres. Optimization was done by fitting experimental data to the software program (Design-Expert (R) 7 trial version). Product batches were subjected to various characterization tests which are mandatory for the development of dosage form. The optimized batch of formulation showed satisfactory yield (82.00 +/- 1.18%) and drug entrapment efficiency (82.15 +/- 1.35%). Particles were of spherical shape, smooth surface and good flowability, and its average particle size is 133.4 +/- 2.27 mu m. The developed optimized batch of microspheres ensured sustained release (>12 h) of ibuprofen. No chemical interaction was observed between ibuprofen and polymer-Eudragit RSPO as evidenced by Fourier transform-infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. In conclusion, development of controlled release drug delivery system of ibuprofen was successfully made. (C) 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.