A biodegradable triblock poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone), denoted PCEC, copolymer was successfully synthesized by ring-opening polymerization of ε-caprolactone, and was characterized by intrinsic viscosimetry, 1H nuclear magnetic resonance, infrared spectroscopy and X-ray diffraction. Copolymer microparticles loaded with ibuprofen were prepared by an oil-in-water (o/w) emulsion solvent evaporation process. In this work, four selected process parameters (shaking speed, time of contact, poly(vinyl alcohol) concentration, and ibuprofen concentration) were adjusted at two different values. For each of the sixteen experimental conditions, repeated twice, the drug encapsulation efficiency of the microspheres was determined. A two level full factorial design method was applied to evaluate the effect of the four factors on the observed responses (encapsulation efficiency) and to determine the optimal conditions for the microencapsulation of the ibuprofen through an accurate statistical protocol. According to the electron micrographs the PCEC microparticles obtained exhibit a spherical shape as shown by electron microscopy. The mean diameter of the microspheres ranged from 90 to 236 μm. Finally, PCL based copolymers has a great interest in the field of microencapsulation of hydrophobic drug such as ibuprofen.