난용성 의약품의 생체이용률 증진을 위한 무정형 초미립자의 조제 : UDCA와 SLS의 혼합분쇄 효과

Amorphous Ultrafine Particle Preparation for Improvement of Bioabailability of Insolube Drugs: Effect of Co-Grinding of UDCA with SLS

  • 정한영 (부산대학교 대학원 학과간 분체공학협동과정) ;
  • 곽성신 (부산대학교 대학원 학과간 분체공학협동과정) ;
  • 김현일 (부산대학교 대학원 학과간 분체공학협동과정) ;
  • 최우식 (부산대학교 대학원 학과간 분체공학협동과정, 부산대학교 제약학과)
  • 발행 : 2002.04.01

초록

The particle size of medicinal materials is an important physical property which affects the pharmaceutical behaviors such as dissolution, chemical stability, compressibility and bioavailability of solid dosage forms. The size reduction of raw pharmaceutical powder is needed to formulize insoluble drugs or slightly soluble drugs and to improve the pharmaceutical properties such as the solubility, the pharmaceutical mixing and the dispersion. The objective of the present study is to evaluate the grinding characteristics of ursodeoxycholic acid(UDCA) as a model of insoluble drugs. The effects of the grinding time and the amount of additive on particle size distribution of ground UDCA were investigated. Grinding of insoluble drug, UDCA and a series of dry co-grinding experiments of UDCA with sodium lauryl sulfate(SLS) as an additive were carried out using a planetary ball mill. It was measured that the median diameter and the particle size distribution of ground products with grinding UDCA and additive SLS by Mastersizer. As a result of co-grinding of UDCA and SLS, the particle size of co-grinding products was decreased more than single grinding one. However, it was observed that co-grinding products were reaggregated to larger particles after 120 min.

키워드

참고문헌

  1. Muler, R. H., Benita, S. and Bohm, B (Eds.) : Emulsions and Nanosuspensions for the Formulation of Poorly Soluble Drugs, Medpharm Scientific, Stuttgart, p. 149 (1998)
  2. Chaumeil, J. C. : Micronization : A method of improving the bioavailability of poory soluble drugs. Meth. Find. Exp. Clin. Pharmacol, 20, 211 (1998)
  3. 平川善行, 原田 淸 :難溶性 醫藥品 結晶の 超微細化 力法の 關發に 關する 硏究 (第2報) オキソリン酸の 超微細化に 及ぼす 種スの 要因, 藥學雜誌, 103, 690 (1983)
  4. 平川善行, 原田 淸 : 難溶性 醫藥品 結晶の 超微細化 力法の 關發に 關する 硏究 (第4報) 超微細化による オキソリン酸の バイオアべイラビリテイの 向上, 藥學雜誌, 103, 1190 (1983)
  5. Japan Powder Technology association: Terminology Dictionary of powder Technology, 2nd Edition, p. 308 (2000)
  6. Liversidge, G. G. and Cundy,K. C. : Particle size reduction for improvement of oral bioavailability of hydrophobic drugs: I. Absolute oral bioavailability of nanocrystalline danazol in beagle dogs, Int. J. Pharm., 125, 91 (1995)
  7. Liversidge, G. G. and Conzentino, P. : Drug particle size reduction for decreasing gastric irritancy and enhancing absorption of naproxen in rats, Int. J. Pharm., 125, 309 (1995)
  8. 難溶性 藥物の 超微粒子化法, 特許 2642486 (1997), 特開平 3-66613 (1991)
  9. 高細英夫, 西岡由紀子, 大澤 孝: 低分子量の水溶性物質との混合粉 砕による難水溶性 澤物の 微細化, 粉體と工業, 24, 53 (1992)
  10. 氣賀澤和雄, 丸山孝一, 田中 洵, 小山 修, 渡部一夫: 醫藥品の生物 學的硏究 (第4報) 2-oxo-3-[4-(1-oxo-2-isoindolinyl)phenyl] butanamide の溶解性および消化質吸收の改善に關する檢討, 藥學雜誌, 101,723 (1981).
  11. Sugara, F. and Shimizu, M. : Jpn. J. Gastroenterol., 71, 75 (1974)
  12. Giunchedi, P., Scalia, S., Maggi, L. and Center, U. : Ursodeoxycholic acid: Improvement of dissolution behaviour and its HPLC determination. Int. J. Pharm., 130, 41 (1996)
  13. Choi, W. S. : Improvement of grinding rate by composite grinding ball size for an ultra-fine grinding mill, 粉體工學會誌 33(9), 747 (1996)
  14. Choi, W. S., Chung, H. Y., Chung, H. Y., Yamamoto, K., Oguchi, T., Tozuka Y., Yonemochi E. and Terada K. : Amorphous and nano-particle preparation for improvement of insoluble drugs bioavailability, The Proceedings of First Asia Particle Technology Symposium(APT 2000), p. 25, Dec. 13-15, Bankok