Determination Of Adsorption Isotherm Of Ketoprofen Enan-Tiomers On Chiralpak Ad Column

Chiral separation is currently a top-class subject in academicresearch as well as pharmaceutical industry, due to the differentpharmacological or toxicological effects of enantiomers. Ketoprofen is acommonly used nonsteroidal antiinflammatory drug (NSAID).S-ketoprofen is used as antipyretic, analgesic and anti-inflammatory drug,R-ketoprofen is effective to prevent periodontal disease, separation ofketoprofen eantiomers is of great significance.Due to the high separation efficiency and reduced pollutions,preparative chromatography especially simulated moving bed （SMB）chromatography has become a promising technique for chiral separation.Accurate determination of adsorption isotherm is necessary for themodeling of preparative chromatography processes.Competitive adsorption isotherms of ketoprofen enantiomers on anamylose-based chiral stationary phase (Chiralpak AD) at6temperaturesin the range of10to35℃were determined in this study by theapplication of the inverse method (IM). Elution profiles of variousoverloaded racemic feed signals were measured on a preparativechromatography column with a precise temperature control system.Parameters of isotherm models were then determined by fitting theexperimental data. Component mass balance in the column was describedby equilibrium-dispersive (ED) model. Isotherm parameters were fittedusing the non-dominated sorting genetic algorithm (NSGA-II) and theLevenberg-Marquardt algorithm (LMA). Three competitive adsorptionisotherm models (Langmuir,5-parameter and6-parameter competitiveBi-Langmuir) were compared based on the fits to experimental data. Bi-Langmuir with5parameters is good enough for fitting.The simulation results given by the Bi-Langmuir isotherm modelwith5parameters agree well with elution profiles measured at varioustemperatures. This study provides fundamental guidance to the futurestudy on ketoprofen enantioseparation using temperature gradient SMB.