화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Clean Technology, Vol.13, No.4, 237-243, December, 2007
Export Citation
디메틸에테르와 초임계이산화탄소의 혼합물에서 Simvastatin 약물의 상거동
Phase Behavior of Simvastatin Drug in Mixtures of Dimethyl Ether and Supercritical Carbon Dioxide
신은경, 오동준, 이병철†
  • 한남대학교 생명나노과학대학 나노생명화학공학과, 대전광역시 유성구 전민동
Eun-Kyoung Shin, Dong-Joon Oh, and Byung-Chul Lee†
  • Department of Chemical Engineering and Nano-Bio Technology, 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 디메틸에테르를 용매로 사용하고 초임계이산화탄소를 역용매로 사용하는 초임계 역용매 재결정법에 의해 약물 미세입자를 제조할 때, 운전조건을 설정하는데 활용될 수 있는 가이드라인을 제공하기 위하여 simvastatin/디메틸에테르 초임계이산화탄소 성분계 혼합물의 상거동을 연구하였다. 가변부피 투시 셀이 장착된 고압 상평형장치를 사용하여 여러 가지 조건에서 성분계 혼합물의 구름점(cloud point)을 측정함으로서 디메틸에테르와 초임계이산화탄소의 혼합용매에서 simvastatin의 용해도를 온도 압력 용매 조성의 함수로 결정하였다. 주어진 온도에서 simvastatin 약물의 용해도는 디메틸에테르의 조성과 압력이 증가할수록 온도가 감소할수록 증가하였다.
Phase behavior of the ternary systems of water-insoluble simvastatin drug, which is well known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dimethyl ether (DME) 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-solvent recrystallization process utilizing DME as a solvent and carbon dioxide as an anti-solvent. The solubilities of simvastatin in the mixtures of DME 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 DME composition in solution and the system pressure increases at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature.
Keywords:초임계 상거동 구름점 심바스타틴 약물 디메틸에테르 이산화탄소 미세입자 재결정
  1. Donsi G, Reverchon E, Pharm. Acta Helv., 66, 170 (1991)
  2. Kerc J, Srcic S, Knez Z, Sencar-Bozic P, Int. J. Pharm., 182, 33 (1999)
  3. Sencar-Bozic P, Srcic S, Knez Z, Kerc J, Int. J. Pharm., 148, 123 (1997)
  4. Kwak SH, Hwang SJ, Lee BC, Yakhak Hoeji (J. Pharm. Soc. Korea), 44, 511 (2000)
  5. Kwak SH, Lee S, Woo JS, Lee BC, Hwang SJ, Yakhak Hoeji (J. Pharm. Soc. Korea), 45, 623 (2001)
  6. Fages J, Lochard H, Letourneau JJ, Sauceau M, Rodier E, Powder Technol., 141(3), 219 (2004)
  7. Ginty PJ, Whitaker MJ, Shakesheff KM, Howdle SM, Materals Today, 8, 42 (2005)
  8. Duarte ARC, Costa MS, Simplicio AL, Cardoso MM, Duarte CMM, Int. J. Pharm., 308, 168 (2006)
  9. Reverchon E, Adami R, J. Supercrit. Fluids, 37(1), 1 (2006)
  10. Yeo SD, Kiran E, J. Supercrit. Fluids, 34(3), 287 (2005)
  11. Perrut M, Jung J, Leboeuf F, Int. J. Pharm., 288, 3 (2005)
  12. Rodier E, Lochard H, Sauceau M, Letourneau JJ, Freiss B, Fages J, Eur. J. Pharm. Sci., 26, 184 (2005)
  13. Song KH, Lee CH, Lim JS, Lee YW, Korean J. Chem. Eng., 19(1), 139 (2002)
  14. Won DH, Kim MS, Lee S, Park JS, Hwang SJ, Int. J. Pharm., 301, 199 (2005)
  15. Lee S, Kim MS, Kim JS, Park HJ, Woo JS, Lee BC, Hwang SJ, J. Microencapsul., 23, 741 (2006)
  16. Miguel F, Martin A, Gamse T, Cocero MJ, J. Supercrit. Fluids, 36(3), 225 (2006)
  17. Huang Z, Sun GB, Chiew YC, Kawi S, Powder Technol., 160(2), 127 (2005)
  18. Thakur R, Gupta RB, Int. J. Pharm., 308, 190 (2006)
  19. Lee JM, Lee BC, Hwang SJ, J. Chem. Eng. Data, 45, 1162 (2000)
  20. Lee BC, Kuk YM, J. Chem. Eng. Data, 47, 367 (2002)
  21. Oh DJ, Lee BC, Hwang SJ, Korean J. Chem. Eng., 23(6), 1009 (2006)
  22. Oh DJ, Lee BC, Hwang SJ, J. Chem. Eng. Data, 52, 1273 (2007)
  23. Oh DJ, Lee BC, Clean Technol., 13(1), 34 (2007)