KSBB Journal

The Korean Society for Biotechnology and Bioengineering (한국생물공학회)
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Removal of Residual Solvents in Paclitaxel by Supercritical Carbon Dioxide

초임계 이산화탄소를 이용한 Paclitaxel의 잔류용매 제거

  • 김진현 (공주대학교 화학공학과) ;
  • 박흥복 ((주)삼양제넥스 생명공학연구소) ;
  • 기은숙 ((주)삼양제넥스 생명공학연구소) ;
  • 강인선 ((주)삼양제넥스 생명공학연구소) ;
  • 최형균 ((주)삼양제넥스 생명공학연구소) ;
  • 홍승서 ((주) 삼양제넥스 생명공학연구소)
  • Published : 2001.06.01
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Abstract

Because of casehardenign effect of amorphous paclitaxel, residual solvents, methylene chloride and emthanol could not be reduced to the maximum value allowed, 600 ppm and 3,000 ppm, in accord with the guidelines issued by the International Conference on Harmonization (ICH, 1997), using rotary evaporation and successive drying in a vacuum oven. However, methylene chloride and methanol were reduced to 486 ppm and 403 ppm, respectively using supercritical $CO_2$ on purified paclitaxel. The optimum pressure and operating time were 80 bar and 30 min at fixed operating temperature ($40^{circ}C$). This approach serves as a novel application of supercritical fluid extraction to remove residual solvents from active pharmaceutical ingredients.

원료 의약품의 경우 정제된 최총제품 내려 잔류용매 제거는 매우 중요하다. 일반적인 진공건조 방법에 의한 제품생산시 case hardening 효과 때문에 잔류용매획 제거가 상당히 어렵다. 본 연구에서는 초임제 이산화탄소를 아용하여 정제된 paclitaxel 내의 methylene chloride와 methanol 의 잔류용매를 효과적으로 제거하였다. 초임계 이산화탄소를 이용하여 $40^{circ}C$, 80 bar에서 30분간 조업하였율 경우 최초 최종제품 내 잔류 용매인 methylene chloride 와 methanol이 각각 5,869 ppm과 2,135 ppm에서 468 ppm과 403 ppm으로 줄어 ICH 규정치를 충분히 만족시킬 수 있다. 이러한 연구 결과는 초임계 유체의 새로운 응용 분야를 개척하고 많은 원료 의약품의 잔류용매 제거에 효과적으로 사용할 수 있을 것으로 사료된다.

Keywords

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