화학공학소재연구정보센터
Clean Technology, Vol.16, No.2, 80-87, June, 2010
초임계유체공정을 이용한 난용성 항진균제의 미세입자 제조
Preparation of Micro- and Submicron-Particles of a Poorly Water-Soluble Antifungal Drug Using Supercritical Fluid Process
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초록
본 연구에서는 초음파가 결합된 초임계유체 입자 제조 기술인 SAS-EM 공정을 이용하여 난용성 항진균제인 이트라코나졸의 미세입자를 제조하였다. 실험에 사용된 SAS-EM 장치의 경우 초음파가 분사노즐에 직접 적용되었다는 점에서 기존의 SAS-EM 공정과 차이가 있으며, 초음파 세기, 공정온도, 용매 등의 여러 공정변수가 미세입자 형성에 미치는 영향을 고찰하였다. 초음파의 세기가 증가할수록 더 작은 크기를 가지는 입자의 생성률이 증가하였으며, SAS-EM 공정으로 제조된 미세입자도 원시료와 마찬가지로 결정구조를 가짐을 확인하였다. 초음파의 영향을 고찰하기 위해 기존의 초임계 ASES 공정과 비교하였으며, SAS-EM 공정에 의해 크기가 더 작은 입자가 형성됨을 확인하였다.
In this study, micro- and submicron particles of itraconazole, a poorly water-soluble antifungal drug, were prepared for improving its aqueous solubility using an ultrasound-assisted supercritical fluid technique, called SAS-EM. The SAS-EM process used in our experiments was different from the conventional SAS-EM in that the ultrasound was applied directly to the spray nozzle. The effect of the ultrasonic power, temperature, and solvent on the formation of itraconazole particles were investigated. Smaller particles were obtained through our SAS-EM process compared with the ASES process, and the mean particle size decreased as the ultrasonic power increased. Our experimental results confirmed that the ultrasound-assisted supercritical fluid process is an efficient method for producing ultrafine particles.
  1. York P, Pharm. Sci. Technol. Today., 2(11), 430 (1999)
  2. Roberts CJ, Debenedetti PG, AIChE J., 48(6), 1140 (2002)
  3. Thote AJ, Gupta RB, Nanomedicine: Nanotech. BioI. Med., 1(1), 85 (2005)
  4. Chattopadhyay P, Gupta RB, Ind. Eng. Chem. Res., 40(16), 3530 (2001)
  5. Chattopadhyay P, Gupta RB, AIChE J., 48(2), 235 (2002)
  6. Gupta RB, Chattopadhyay P, "Method of Fonning Nanoparticles and Microparticles of Controllable Size Uing Nanoparticles and Microparticles of Controllable Size Uing (2003)
  7. Lee LY, Wang CH, Smith KA, J. Control. Release., 125(2), 96 (2008)
  8. Chattopadhyay P, Gupta RB, Int. J. Pharrn., 228(1-2), 19 (2001)
  9. Fromtling RA, "Recent Trends in the Discovery, Development and Evaluation of Antifungal Agents," J. R. Prous Science Publishers, 223 (1987)
  10. Carretier E, Badens E, Guichardon P, Boutin O, Charbit G, Ind. Eng. Chem. Res., 42(2), 331 (2003)
  11. Jones AG, "Crystallization Process Systems," ButterworthHeinemmm, 137 (2002)
  12. Shekunov BY, Baldyga J, York P, Chem. Eng. Sci., 56(7), 2421 (2001)
  13. Lang RJ, J. Acoust. Soc. Am., 34, 6 (1962)
  14. Topp MN, J. Aeros. Sci., 4(1), 17 (1973)
  15. Rajan R, Pandit AB, Ultrasonics., 39(4), 235 (2001)
  16. Avvaru B, PatH MN, Gogate PR, Pandit AB, Ultrasonics., 44(2), 146 (2006)
  17. Liversidge EM, Liversidge GG, Cooper ER, Eur. J. Pharm. Sci., 18(2), 113 (2003)
  18. Hu J, Johnston KP, Williams III, RO, Eur. 1. Pharm. BioPharm., 20(3), 295 (2003)
  19. Willams III RO, Johnston KP, Young TJ, Rogers TLZY, Hu J, "Process for Production of Nanoparticles and Microparticles by Spray Freezing into Liquid," US Patent No. 6,862,890 (2005)
  20. Johnston KP, Willams III, RO, Young TJTL, Xiaoxia C, "Preparation of Drug Particles Using Evaporation Precipitation into Aqueous Solutions," US Patent No. 6,756,062 (2004)
  21. Sheehan DJ, Hitchcock CA, Sibley CM, Clin Microbial. Rev., 12(1), 40 (1999)
  22. Warnock DW, J. Antimicrob. Chemoth., 24, 275 (1989)
  23. Barrett AM, Dehqhani F, Foster NR, Pharm. Res., 25(6), 1274 (2008)
  24. Werling JO, Debenedetti PG, J. Supercrit. Fluids, 18(1), 11 (2000)
  25. Martin A, Cocero MJ, J. Supercrit. Fluids, 32(1-3), 203 (2004)
  26. Kim YH, Sioutas C, Fine P, Shing KS, Powder Technol., 182(3), 354 (2008)
  27. Reverchon E, Della Porta G, Falivene MG, J. Supercrit. Fluids, 17(3), 239 (2000)