This work presents the experimental and simulation results obtained for the optimization of the mobile phase composition for the preparative separation of flurbiprofen enantiomers by liquid chromatography using an amylose-based chiral stationary phase (Chiralpak AD). The experimental work carried out includes solubility and adsorption isotherm measurements and pulse and breakthrough experiments under preparative conditions. The simulation work predicts the operation of a simulated moving bed (SMB) system for the separation of flurbiprofen enantiomers to compare the productivity and solvent consumption performances, for the different mobile phase compositions and using the experimental data obtained. This paper presents a new and different case study (flurbiprofen) of the one recently reported by the authors (ketoprofen enantiomers [A. Ribeiro, N. Graca, L. Pais, A. Rodrigues, Preparative separation of ketoprofen enantiomers: choice of mobile phase composition and measurement of competitive adsorption isotherms, Sep. Purif. Technol. 61 (2008) 375-383]), to clearly show that the optimization of the mobile phase composition for preparative chiral separation requires an individualized study, since different results are obtained even for enantiomers systems of the same family. (C) 2009 Elsevier B.V. All rights reserved.