화학공학소재연구정보센터
Journal of Chemical Engineering of Japan, Vol.30, No.6, 1005-1012, 1997
Continuous optical resolution of antihypertensive drug by column chromatography
A chromatography system for manufacturing a chiral antihypertensive drug, namely semotiadil fumarate, was studied. The racemate of semotiadil fumarate needs to be completely resolved because high purity is needed for the compound's use as medicine. For this reason, high performance liquid chromatography (HPLC) was adopted. To supply the requirement, a continuous system is needed. In this case, a system having plural batch columns injected sequentially was employed. To design the system, the number of columns needed was predicted by simulation. The result was in good agreement with experimental results. To fractionate the racemate completely, it was ound that the valves in the column outlets were related to their absorbance. It was found that these valves worked steadily when the disturbances in the absorbance detected were removed using first-order lag conversion. On the basis of the above findings, a system was designed and actually made. The eluate was passed through the detector only when it changed from one enantiomer to another, so the system was provided with only two detectors. The influences of some pipe puddles were large; however, with a wash system devised to complement the system, the racemate of semotiadil fumarate was separated continuously and completely. In this system, the purity, activity, and recovery are similar to that of a single column. However, because the throughput is larger, the system is useful for making the antihypertensive drug.