Development Of The Two Chromatographic Columns Switching System And Its Application In The Separation Of Chiral Drugs

The trend of Phannaceutcal industry toward cornrnercializing chiral drugs as Pureenantiomers enhances the need of efficieni processes for the separation of racemates.Simulated moving bed chromatograPhy has attracted much .interest from thephannaceutical industry, because of the advtages of its contnuous operation overthe more conveniional batch imPlementations of preparative chromatograPhy.Simulated moving bed chromatograPhy can also save large amoun of eluent andadsorbeflt, and achieve high resolution and purity.The other poweffol chromatograPhic technique in separation of chiral drugs isclosed-loop recycling chromatograPhy. Recycling chromatograPhy is similar tosimulated moving bed chromatograPhy in that sample is injected into the interior ofthe profile. Difference from simulated moving bed chIomatograPhy lies in that itsprocess, although repetitive, is not continuous.Based on the separation principles of simulated moving bed chromatograPhy andclosed-loop recycling chLromatography,the two cliromatograPhic columns switchingsystem is designed and developed originally. Efficient usage of stationary phase andsaving of mobile phase can also be obtained in this system. In view of usage ofstationary phase, this system is more aPproximate to simulated moving bedchIomatograPhy than closed-loop recycling chromatograPhy. As the saving ofmobile phase is considered, it approximates to simulated moving bedchromatograPhy too. This system is obviously cheaPer than simulated moving bedchromatograPhy as well as closed-loop recycling chromatograPhy, although itsadvantages show up practically. TO implement the aUtomation of the twochromatograPhic columns switching system, the control sofiware fOr this system hasbeen designed. The timing control and automatic conirol were implementedcreatively in this software. The whole system has been working robustly.In testing the performance of two chromatograPhic columns switching system,separation of some chiral samp1es has been carried out on it. As a result, high purityseparation of DNP-threonine. DNP-glutamic acid and warfarin has been achievedsuccessfully. The result of experiments indicated that the operation of the twochromatographic columns switching system can reach a stable state,after the firstsuccessive two repeats, and the system can run well in gear under the timingcontrol .In the same condition, separation of warfarin has been perfOrmed on 10cm X1. 0cm I. D. 0C chiral columns as well as l5cmX l. 5cm I. D. 0C chiral columns.Efficiency of the later sepndion is similar to tha of the fOrmer.One method to enhance product arnoun on the separation of chiral drugs is toincrease the concentration of sample, which leads to the separation ofchiral drigs inthe condition Wth non-linear adsorption isortherm. In this context, the Langmuircompetitive adsorption isotherm of warfarin adsorbed on 20 ll m OC chiral colunmwas obtained by frontal analysis, and the numerical simulation of the separation ofwarfarin on tWo chromatograPhic colunms switching system was also cdried out.The result of simulation is well consistent with that of exPerimot.