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  • 标题:Physicochemical Evaluation and Developability Assessment of Co-amorphouses of Low Soluble Drugs and Comparison to the Co-crystals
  • 本地全文:下载
  • 作者:Katsuhiko Yamamoto ; Taro Kojima ; Masatoshi Karashima
  • 期刊名称:Chemical and Pharmaceutical Bulletin
  • 印刷版ISSN:0009-2363
  • 电子版ISSN:1347-5223
  • 出版年度:2016
  • 卷号:64
  • 期号:12
  • 页码:1739-1746
  • DOI:10.1248/cpb.c16-00604
  • 语种:English
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:

    To judge the developability and analyze functional mechanism of co-amorphouses, we investigated the physicochemical properties of co-amorphouses and compare the properties with the co-crystals having the same drug and counters. Co-amorphous compounds are a novel approach to improve the physicochemical properties of drugs. A co-amorphous is in an amorphous solid state allowing non-ionic interactions between drug molecules and counter molecules. The co-amorphous compounds composed of itraconazole (ITZ) with the organic carboxyl acid, fumaric acid (FA) or L-tartaric acid (TA), were prepared by mechanical grinding. Potential interactions within ITZ-FA co-amorphous were assessed by Raman spectroscopy. ITZ-FA co-amorphous was not crystallized as the co-crystal or as a single ITZ crystal, suggesting that the amorphous state, like the amorphous solid dispersion, was physically stable and that ITZ-FA co-amorphous was also chemically stable. In contrast, no clear interactions were observed within ITZ-TA co-amorphous, and the co-amorphous was physically stable but chemically unstable. The solubility of the co-amorphous state was much higher than those of ITZ crystal and the co-crystals and was almost identical to that of amorphous ITZ. A co-amorphous compound like ITZ-FA co-amorphous might be feasible to implement in the development of solid drug products and bring some merits compared to the co-crystals, and the function is governed by the interaction between a drug and a counter. The co-amorphous approach may be an effective strategy for drug development and can contribute to the production of novel drugs with improved functions.

  • 关键词:co-amorphous;co-crystal;stability;solubilization;interaction;itraconazole
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