Laboratory of Separation and Reaction Engineering, Associate Laboratory LSRE/LCM, School of Technology and Management, Polytechnic Institute of Bragança, Campus de Santa Apolónia, Apartado 1134, 5301-857 Bragança, Portugal.
Chirality. 2011 Sep;23(8):602-11. doi: 10.1002/chir.20978. Epub 2011 Jul 13.
This study presents the chiral resolution of flurbiprofen enantiomers by preparative liquid chromatography using the simulated moving bed (SMB) technology. Flurbiprofen enantiomers are widely used as nonsteroidal anti-inflammatory drugs, and although demonstrate different therapeutic actions, they are still marketed as a racemic mixture. The results presented here clearly show the importance of the selection of the proper solvent composition for the preparative separation of flurbiprofen enantiomers. Chiral SMB separation is carried out using a laboratory-scale unit (the FlexSMB-LSRE®) with six columns, packed with the Chiralpak AD® stationary phase (20 μm). Results presented include the experimental measurement of equilibrium and kinetic data for two very different solvent compositions, a traditional high hydrocarbon content [10%ethanol/90%n-hexane/0.01% trifluoroacetic acid (TFA)] and a strong polar organic composition (100%ethanol/0.01%TFA). Experimental data, obtained using the two mobile phase compositions, are used to predict and optimize the SMB operation. After selecting 10%ethanol/90%n-hexane/0.01%TFA as the most appropriate solvent composition, three feed concentrations of racemic flurbiprofen were considered. Using 40 g/l of racemic flurbiprofen feed solution, the purities for both outlet streams were above 99.4%, the productivity was 13.1 g(feed) /(L(bed) h), and a solvent consumption of 0.41 L(solvent) /g(feed) was achieved.
本研究通过模拟移动床（SMB）技术的制备液相色谱法对氟比洛芬对映异构体进行了手性拆分。氟比洛芬对映异构体广泛用作非甾体抗炎药，尽管表现出不同的治疗作用，但仍以外消旋混合物的形式上市。这里呈现的结果清楚地表明了选择适当溶剂组成对制备性分离氟比洛芬对映异构体的重要性。手性 SMB 分离使用带有六个柱的实验室规模单元（FlexSMB-LSRE®）进行，用 Chiralpak AD®固定相（20 μm）填充。呈现的结果包括两种非常不同溶剂组成的平衡和动力学数据的实验测量，一种传统的高烃含量[10%乙醇/90%正己烷/0.01%三氟乙酸（TFA）]和一种强极性有机组成（100%乙醇/0.01%TFA）。使用两种流动相组成获得的实验数据用于预测和优化 SMB 操作。在选择 10%乙醇/90%正己烷/0.01%TFA 作为最合适的溶剂组成后，考虑了三种外消旋氟比洛芬的进料浓度。使用 40 g/l 的外消旋氟比洛芬进料溶液，两个出口流的纯度均高于 99.4%，产率为 13.1 g（进料）/（L（床）h），溶剂消耗为 0.41 L（溶剂）/g（进料）。
