The Study Of Seperation Process Of Ketoprofen Enantiomers On Temperature Gradient Of Simulated Moving Bed

Compared to the high performance liquid chromatography (HPLC), the continuous simulated moving bed (SMB) chromatography, which was extensively applied to separate and purify oils, sugars, and drugs, can effectively decrease the solvent consumption and improve the production capacity. Ketoprofen is one of the commonly used nonsteroidal anti-inflammatory drugs (NSAID), and its active component is the S-ketoprofen. The other form, R-ketoprofen, has a preventive effect in periodontitis, gingivitis and other diseases. Actually, ketoprofen on the market mostly exists as the racimic form。Therefore, the separation and purification of ketoprofen enantiomers are of great significance.The objective of this research is to achieve the large scale production of ketoprofen enantiomers. In this work, the adsorption behavior of ketoprofen enantiomers on Chirapak AD column was investigated and the temperature gradient-simulated moving bed separation technique was developed. Inverse method(IM) was used to study the temperature effects on the competitive adsorption equilibrium of ketoprofen enantiomers on a preparative Chiralpak AD column.Linear elution curves of ketoprofen enantiomers at various temperatures were acquired by using the HPLC. Based on these data, mass transfer coefficient, number of theoretical plates and the Henry constants were determined. Mass transfer coefficients of two enantiomers are different but both strongly depend on the temperature variation. Overloaded band profiles of ketoprofen enantiomers were acquired at different temperatures. These profiles were fitted by using the Langmuir,linear-Langmuir and bi-Langmuir isotherm models respectively. After comparing,the bi-Langmuir model provides the best fitting result. This model was then corrected with three extra parameters which represent the non-selective adsorption enthalpy and selective adsorption enthalpy of the ketoprofen enantiomers. Finally,the corrected model was applied to simultaneously fit three overloaded band profiles obtained at different temperatures to determine a group of bi-langmuir parameters.In conclusion, separation of ketoprofen enantiomers on temperature-gradient simulated moving bed was successfully achieved and optimized in this work. The optimum operation conditions were obtained and the influence of the temperature-gradient SMB on separation performance was clarified. This study also provides fundamental guidance to the future research of chiral drugs separation using temperature-gradient SMB.