Glass-State Amorphous Salt Solids Formed by Freeze-Drying of Amines and Hydroxy Carboxylic Acids: Effect of Hydrogen-Bonding and Electrostatic Interactions

• Kadoya Saori

  Faculty of Pharmaceutical Sciences, Toho University

• Izutsu Ken-ichi

  National Institute of Health Sciences

• Yonemochi Etsuo

  Faculty of Pharmaceutical Sciences, Toho University

• Terada Katsuhide

  Faculty of Pharmaceutical Sciences, Toho University

• Yomota Chikako

  National Institute of Health Sciences

• Kawanishi Toru

  National Institute of Health Sciences

抄録

We studied effect of molecular interactions on the physical properties of binary freeze-dried solids and frozen aqueous solutions using model chemicals containing various functional groups (amino, carboxyl, hydroxyl). Thermal analysis of frozen solutions containing alkyl diamines and hydroxy di- or tricarboxylic acids showed thermal transitions (T_g′: glass transition of maximally freeze-concentrated phase) at temperatures higher than those of the individual solutes. A binary frozen solution containing 80 mM 1,3-diamino-2-hydroxypropane (single-solute T_g′<−60 °C) and 120 mM citric acid (single-solute T_g′: −55.0 °C) made the transition at −30.8 °C. The molecular weight of the solutes had smaller effects on the transition temperatures of the frozen mixture component solutions. Lyophilization of some high T_g′ mixture frozen solutions (e.g., 1,3-diamino-2-hydroxypropane and citric acid) resulted in cake-structure amorphous solids with glass transition temperatures (T_g) higher than those of the individual components. Networking of intense hydrogen-bondings and electrostatic interactions between the heterogeneous molecules through the multiple functional groups was suggested to reduce the component mobility in the amorphous freeze-concentrated phase and the freeze-dried solids. Controlling the interactions should be a key to optimizing the physical properties of multi-component amorphous freeze-dried pharmaceutical formulations.

収録刊行物

• ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ

  ＣＨＥＭＩＣＡＬ　＆　ＰＨＡＲＭＡＣＥＵＴＩＣＡＬ　ＢＵＬＬＥＴＩＮ 56 (6), 821-826, 2008

  公益社団法人 日本薬学会

キーワード

• freeze-drying
• glass solid
• thermal analysis
• molecular interaction
• salt

詳細情報

• CRID: 1390282679146754432
• NII論文ID: 110006684281
• NII書誌ID: AA00602100
• DOI: 10.1248/cpb.56.821
• ISSN: 13475223
• ISSN: 00092363
• NDL書誌ID: 9508861
• Web Site: http://id.ndl.go.jp/bib/9508861
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I9508861
• Web Site: http://www.jstage.jst.go.jp/article/cpb/56/6/56_6_821/_pdf
• 本文言語コード: en
• データソース種別:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
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