Formulation, Characterization and Hypersensitivity Evaluation of an Intravenous Emulsion Loaded with a Paclitaxel-Cholesterol Complex

• Xia Xue-Jun

  Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College

• Guo Rui-Fang

  Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College

• Liu Yu-Ling

  Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College

• Zhang Peng-Xiao

  Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College

• Zhou Cui-Ping

  Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College

• Jin Du-Jia

  Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College

• Wang Ren-Yun

  Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College

抄録

The objective of this paper was to develop a novel Cremophor-free, autoclave stable, intravenous emulsion for paclitaxel (PACE). A paclitaxel–cholesterol complex was used as the drug carrier to improve the solubility of paclitaxel in the oil phase of emulsions. The complex and PACE were prepared by rotary evaporation and high-pressure homogenization, respectively. Effects of oil phases, emulsifiers and pH values on the characteristics of PACE were investigated. PACE was characterized with regard to its appearance, morphology, osmolality, pH value, particle size, zeta potential, encapsulation efficiency and stability. Hypersensitivity was evaluated by guinea pig hypersensitivity reaction. The final formulation was composed of the complex, soybean oil, medium-chain triglyceridel, soybean lecithin, poloxamer 188 and glycerol. The resulting PACE had an encapsulation efficiency of 97.3% with a particle size of 135 nm and a zeta potential of −38.3 mV. Osmolality and pH of the formulation were 383 mOsmol/kg and 4.5, respectively. The formulation survived autoclaving at 115 °C for 30 min and remained stable for at least 12 months at 6 °C. PACE also exhibited a better tolerance than an equal dose of Cremophor-based paclitaxel injection in guinea pigs, as no obvious hypersensitivity reaction was observed. These results suggested that PACE has a great potential for industrial-scale production and clinical applications.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 59 (3), 321-326, 2011

  公益社団法人 日本薬学会

キーワード

• paclitaxel
• emulsion
• complex
• characterization
• stability
• hypersensitivity

詳細情報

• CRID: 1390001204172724480
• NII論文ID: 130000648939
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.59.321
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 10990461
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10990461
• Web Site: http://www.jstage.jst.go.jp/article/cpb/59/3/59_3_321/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2012000171
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可