화학공학소재연구정보센터
홈 로그인 로그아웃 연락처 사이트맵
Clean Technology, Vol.26, No.1, 1-6, March, 2020
DOI10.7464/ksct.2020.26.1.1  Export Citation
초임계 유체를 이용한 약물이 담지된 PAc-β-CD 나노 입자의 친환경적인 제조
A Green Preparation of Drug Loaded PAc-β-CD Nanoparticles from Supercritical Fluid
장민기, 김용훈, 김동우1, 이시윤, 임권택†
  • 부경대학교 융합디스플레이공학과, 48513 부산광역시 남구 용소로 45
  • 1한국과학기술연구원 전북분원 복합소재기술연구소, 55324 전북 완주군 봉동읍 추동로 92
Min Ki Jang, Yong Hun Kim, Dong Woo Kim1, Si Yun Lee, and Kwon Taek Lim†
  • Department of Image Science & Engineering, Pukyong National University, Daeyeon-dong, Nam-gu, Busan 48513, Korea
  • 12Composite Materials Application Research Center, Institute of Advanced Composite Materials, Korea Institute of Science and Technology (KIST), Chudong-ro 92, Bongdong-eup, Wanju-gun, Jeonbuk 55324, Korea
E-mail:
초록
초임계 용액 급속팽창법(rapid expansion of supercritical solution, RESS)으로 몰시도민(molsidomine, MOL) 약물이 로딩 된 퍼아세틸-β-사이클로덱스트린(PAc-β-CD) 나노 입자를 제조하였다. 입자는 초임계 용액을 공기 중으로 급속하게 팽창시켜 제조하였다. MOL과 PAc-β-CD (0.5, 1 wt%)의 농도, 추출 온도(45 ~ 60 ℃), 모세관 노즐의 길이(5 ~ 20 mm) 및 내경(Inner diameter, ID) (50 ~ 150 μm), 그리고 분사 거리의 변화에 따라 형성된 입자의 크기와 모폴로지를 조사하였다. MOL과 PAc-β-CD의 상호작용을 1H-NMR 분광법으로 확인하였고, 입자 크기는 주사 전자 현미경으로 측정하였다. 온도를 45 ℃에서 60℃로 올리거나 노즐 내경을 150 μm에서 50 μm로 줄이면 입자 평균 크기가 증가하였으며, 반면에 일정한 압력(34.5 MPa)과 온도(45 ℃)에서 분사 거리를 늘리면 입자 평균 크기가 감소하는 효과를 나타내었다. 0.5 wt%의 PAc-β-CD 농도로서 초임계 공정을 진행한 결과, 모세관의 길이가 짧고(5 mm) 내경이 작은(50 μm) 조건에서 크기가 가장 작은(165 nm) 입자가 얻어졌다. 제조한 나노 입자는 오일 내에서 분산성과 용해도가 증가하였으며, 포접체 입자에서 MOL이 방출되는 시간이 지연되는 것을 확인하였다.
Rapid expansion of supercritical solution (RESS) process was used to make molsidomine (MOL) loaded peracetyl-β -cyclodextrin (PAc-β-CD) nanoparticles, which were collected into the air. The effect of the concentration of the drug PAc-β-CD (0.5 and 1 wt%), extraction temperature (45 ~ 60 ℃), nozzle length (5 ~ 20 mm) and internal diameter (ID) (50 ~ 150 μm) of a capillary, and spray distance on the particle size and morphology of the resulting particles were investigated. The interaction of a drug and PAc-β-CD was confirmed by 1H-NMR spectroscopy while the particle size was measured by means of a scanning electron microscope. It was found that increasing the temperature from 45 ℃ to 60 ℃ and decreasing the nozzle diameter from 150 μm to 50 μm had an increasing effect on the average particle size, while increasing the spray distance led to a decrease in the average particle size at a constant pressure of 34.5 MPa and temperature of 45 ℃. With 0.5 wt% of PAc-β-CD, the capillary nozzle of short length (5 mm) and small ID (50 μm) gave the smallest size (165 nm). The obtained nanoparticles showed increased dispersity and solubility in oil. The oil suspension of the inclusion complex showed increased sustainability, which can increase the in-vitro controlled release time of the drug.
Keywords:Supercritical carbon dioxide;Rapid expansion of supercritical solution;Peracetyl-β-cyclodextrin;Inclusion complex;Controlled drug release
  1. Lee MY, Ganpathy HS, Lim KT, J. Phys. Chem. Solids, 71, 630 (2010)
  2. Ganapathy HS, Lee MY, Park C, Lim KT, J. Fluor. Chem., 129, 1162 (2008)
  3. Ganapathy HS, Woo WH, Gal YS, Lim KT, Key Eng. Mater., 342, 489 (2007)
  4. Sultana T, Jung JM, Hong SS, Lee WK, Gal YS, Kim HG, Lim KT, J. Incl. Phenom. Macrocycl. Chem., 72, 207 (2012)
  5. Lim KT, Ganapathy HS, Lee MY, Yuvaraj H, Lee WK, Heo H, J. Fluor. Chem., 127, 730 (2006)
  6. Lim KT, Subban GH, Hwang HS, Kim JT, Ju CS, Johnston KP, Macromol. Rapid Commun., 26(22), 1779 (2005)
  7. Kim JH, Ganapathy HS, Hong SS, Gal YS, Lim KT, J. Supercrit. Fluids, 47(1), 103 (2008)
  8. Kim YH, Choi HW, Kang KM, Karakin A, Lim KT, Clean Technol., 24(3), 157 (2018)
  9. Kim DW, Heo H, Lim KT, Clean Technol., 23(4), 357 (2017)
  10. Ganapathy HS, Kim JH, Hong SS, Lim KT, Int. J. Biomed. Nanosci. Nanotechnol., 8, 4707 (2008)
  11. Yim JH, Kim WS, Lim JS, J. Supercrit. Fluids, 82, 168 (2013)
  12. Huang Z, Sun GB, Chiew YC, Kawi S, Powder Technol., 160(2), 127 (2005)
  13. Charpentier PA, Jia M, Lucky ARA, AAPS. PharmSciTech., 9, 39 (2008)
  14. Bolten D, Turk M, J. Supercrit. Fluids, 62, 32 (2012)
  15. Hezave AZ, Aftab S, Esmaeilzadeh F, J. Supercrit. Fluids, 55(1), 316 (2010)
  16. Turk M, Bolten D, J. Supercrit. Fluids, 55(2), 778 (2010)
  17. Asghari I, Esmaeilzadeh F, Int. J. Pharm., 433, 149 (2012)
  18. Baseri H, Lotfollahi MN, Powder Technol., 253, 744 (2014)
  19. Lin PC, Su CS, Tang M, Chen YP, J. Supercrit. Fluids, 72, 84 (2012)
  20. Hiendrawan S, Veriansyah B, Tjandrawinata RR, Procedia Chem., 9, 257 (2014)
  21. Chingunpitak J, Puttipipatkhachorn S, Drug Dev. Ind. Pharm., 34, 609 (2008)
  22. He S, Zhang Z, Xu F, Zhang S, Lei Z, Chem. Pharm. Bull., 58(2), 154 (2010)
  23. Su CS, Tang M, Chen YP, J. Supercrit. Fluids, 59, 69 (2009)
  24. Paliwal R, Babu RJ, Palakurthi S, AAPS. PharmSciTech., 15(6), 1527 (2014)
  25. Hiendrawan S, Veriansyah B, Tjandrawinata RR, J. Ind. Eng. Chem., 20(1), 54 (2014)