화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Clean Technology, Vol.13, No.1, 34-45, March, 2007
Export Citation
디클로로메탄과 초임계 이산화탄소의 혼합용매에서 Simvastatin 약물의 상거동과 초임계 역용매 공정을 이용한 Simvastatin 약물 미세입자의 제조
Phase Behavior of Simvastatin Drug in Mixtures of Dichloromethane and Supercritical Carbon Dioxide and Microparticle Formation of Simvastatin Drug Using Supercritical Anti-Solvent Process
오동준, 이병철†
  • 한남대학교 생명나노과학대학, 305-811 대전광역시 유성구 전민동 461-6
Dong-Joon Oh, and Byung-Chul Lee†
  • Department of Chemical Engineerign and Nano-Bio Technmology, Hannam University, 461-6 Jeonmin-dong, Yuseong-gu, Daejeon 305-811, Korea
E-mail:
초록
고지혈증 치료제로 잘 알려져 있는 난용성 약물인 심바스타틴(simvastatin)을 대상으로 디클로로메탄을 용매로 사용하고 초임계 이산화탄소를 역용매로 사용하는 초임계 역용매 재결정법에 의해 약물 미세입자를 제조할 때, 운전 조건을 설정하는데 활용될 수 있는 가이드 라인을 제공하기 위하여 simvastatin/디클로로메탄/초임계 이산화탄소 3성분계 혼합물의 상거동을 연구하였다. 가변부피 투시 셀이 장착된 고압 상평형 장치를 사용하여 여러 가지 조건에서 3성분계 혼합물의 구름점(cloud point)을 측정함으로서 디클로로메탄과 초임계 이산화탄소의 혼압용매에서 simvastatin의 용해도를 온도, 압력, 용매 조성의 함수로 결정하였다. 주어진 온도에서 Simvastatin 약물의 용해도는 디클로로메탄의 조성과 압력이 증가할수록 온도가 감소할수록 증가하였다. 상거동 데이터를 바탕으로 교반기가 설치된 실린더 모양의 고압 용기에서 초임계 역용매 재결정 공정을 이용하여 simvastatin 약물을 미세입자로 제조하는 연구를 수행하였다. 운전 조건인 압력 (8 ~12 MPa), 온도 (303.15 K, 313.15 K), 이산화탄소 공급 속도, 교반 속도 (최대 3,000 rpm)를 변화시키면서 simvastatin 미세입자를 제조함으로써 재결정되는 약물 입자의 크기와 모양에 미치는 공정 변수들의 영향을 관찰하였다.
Phase behavior of the ternary systems of water-insoluble simvastatin drug, which is well known to be effective durgs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane and supercritical carbon dioxide was investigated to present a guideline of establishing operating conditions in the particle formation of the drugs by a supercritical anti-sovent recrystallization process utilizing dichloromethane as a solvent and carbon dioxide as and anti-sovent. The solubilities of simvastatin in the mixtures of dichloromethane and carbon dioxide were determined as functions of temperature, pressure and solvent composition by measuring the cloud points of the ternary mixtures at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility of the drug increased as the dichloromethane composition in solution and the system pressure inreases at a fixed temperature. A lower solubility of the drug was dbtained at a higher temperature. The second half of this work is focused on the particle formation of the simvastatin drug by a supercritical anti-solvent recrystallization process in a cylindrical high-pressure vessel equipped with an impeller. Microparticles of the simvastatin drug were prepared as functions of pressure (8 MPa to 12 MPa), temperature (303.15 K, 313.15 K), feed flow rate of carbon dioxide, and stirring speed (up to 3000 rpm), in order to observe the effect of those process parameters on the size and shape of the drug microparticles recrystallized.
Keywords:초임계이산화탄소;상거동;구름점;미세입자;재결정;심바스타틴;약물;티클로로메탄
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