약학회지 (YAKHAK HOEJI)

  • 제49권4호
  • /
  • Pages.268-274
  • /
  • 2005
  • /
  • 0377-9556(pISSN)
  • /
  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

나노입자수송시스템을 이용한 파클리탁셀 정맥주사제의 제조 및 평가

Preparation and Evaluation of Paclitaxel Nano-particle Delivery System for Parenteral Formulations

  • Jeon Il-Soon (College of Pharmacy, Chungnam National University) ;
  • Kim Jeong-Soo (College of Pharmacy, Chungnam National University) ;
  • Lee Gye-Won (Department of Pharmaceutical Engineering, Konyang University) ;
  • Jee Ung-Kil (College of Pharmacy, Chungnam National University)
  • 발행 : 2005.08.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Paclitaxel is an effective antineoplastic agent against ovarian, colon and breast tumors. But there have been many difficulties to formulate this drug due to the extremely low aqueous solubility. Paclitaxel is currently formulated in a vehicle composed of Cremophor EL and absolute ethanol mixture which is $5\~20$ fold diluted in normal saline or $5\%$ dextrose solution before I.V. injection. However, this formulation has many problems such as allergic reactions and drug precipitation on aqueous dilution. To overcome these problems, we prepared the micelle and microemulsion systems for parenteral administration of paclitaxel by using glycofurol, $Soluto^{(R)}lHS$ 15 and oleic acid. Phase diagram, pH-rate stability, particle size distributions and pharmacokinetics of the systems were studied. Micelles and microemulsions formulated as nano-particle delivery system were physically and chemically stable. Therefore, these formulations might be the promising alternative candidate for the parenteral delivery of paclitaxel.

키워드

참고문헌

  1. Wacher, V. H., Silverman, J. A., Zhang, Y. and Benet, L. Z. : Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J. Pharm. Sci. 87, 1322 (1998) https://doi.org/10.1021/js980082d
  2. Gelderblom, H., Verweij, J., Nooter, K. and Sparreboom, A. : Cremophor EL : the drawbacks and advantages of vehicle selection for drug formulation. Eur. J. Cancer 37, 1590 (2001) https://doi.org/10.1016/S0959-8049(01)00171-X
  3. Trissel, L. A. : Handbook on Injectable Drugs 11th ed., American Society of Health-System Pharmacists, Inc., Bethesda, p. 1003 (2001)
  4. Spiegelberg, H., Schlapfer, R., Zbinden, G. and Studer, A. : A new injectable solvent (Glycofurol). Arzneimittel-Forschung 6, 75 (1956)
  5. Vromans, H. and Moolenaar, F. : Effect of solvents on rectal absorption rate of paracetamol in man : an in vitro approach. Int. J. Pharm. 26, 5 (1985) https://doi.org/10.1016/0378-5173(85)90195-4
  6. Tauboll, E., Lindstrom, S., Klem, W and Gjerstad, L. : A new injectable carbamazepine solution - antiepileptic effects and pharmaceutical properties. Epilepsy Res. 7, 59 (1990) https://doi.org/10.1016/0920-1211(90)90054-Y
  7. Ran, Y., Zhao, L., Xu, Q. and Yalkowsky; S. H. : Solubilization of cyclosporin A. AAPS PharmSciTech 2, article 2 (2001)
  8. Bechgaard, E., Gizurarson, S. and Hjortkjaer, R. K. : Solubilization of various benzodiazepines for intranasal administration, a pilot study. Pharm. Dev. Technol. 2, 293 (1997) https://doi.org/10.3109/10837459709031449
  9. 배준호, 박은석, 지상철 : 수용액중의 비페닐디메칠디카르디카르복실레이트의 가용화. 약제학회지 27, 199 (1997)
  10. 이종화, 박선영, 김동우, 조미편, 조인숙, 이계원, 박목순, 지웅길 : 마이크로에멀젼을 이용한 프로포폴 주사제의 개발 및 평가. 약학회지 46, 337 (2002)
  11. Corswant, C. V., Thoren, P. and Engstrom S. : Triglyceridebased microemulsion for intravenous administration of sparingly soluble substances. J. Pharm. Sci. 87, 200 (1998) https://doi.org/10.1021/js9702980
  12. Trotta, M., Cavalli, R., Ugazio, E. and Gasco, M. R. : Phase behaviour of microemulsion systems containing lecithin and lysolecithin as surfactants. Int. J. Pharm. 143, 67 (1996) https://doi.org/10.1016/S0378-5173(96)04688-1
  13. Gee, R. P. : Oil-in-water microemulsions from association structures of surfactant, water and aminosilicone polymer oil. Colloids and Surfaces 137, 91 (1998) https://doi.org/10.1016/S0927-7757(97)00345-2
  14. Dordunoo, S. K. and Burt, H. M. : Solubility and stability of taxol : effects of buffers and cyciodextrins. Int. J. Pharm. 133, 191 (1996) https://doi.org/10.1016/0378-5173(96)04443-2
  15. Laia, C. A. T., Brown, W., Almgren, M. and Costa, S. M. B. : Light scattering study of water-in-oil AOT microemulsions with poly(oxy)ethylene. Langmuir. 16, 465 (2000) https://doi.org/10.1021/la990684s
  16. Lehner, D., Lindner, H. and Glatter, O. : Determination of the translational and rotational diffusion coefficients of rodlike particles using depolarized dynamic light scattering. Langmuir. 16, 1689 (2000) https://doi.org/10.1021/la9910273
  17. XU, Q., Trissel, L. A. and Martinez, J. F. : Stability of paclitaxel in 2% dextrose injection or 0.9% sodium chloride injection at 4, 22, or 32 DGC. Am. J. Hasp. Pharm. 51, 3058 (1994)