薬剤製剤の配合のためのダイナミック核極化強化NMRスペクトロスコピー
Aaron J Rossini1, Cory M Widdifield, Alexandre Zagdoun
1Centre de RMN à Trés Hauts Champs, Institut de Sciences Analytiques, Université de Lyon (CNRS/ENS Lyon/UCB Lyon 1) , 69100 Villeurbanne, France.
Journal of the American Chemical Society
|January 14, 2014
まとめ
動的核偏振 (DNP) 固体NMRは,製薬成分の詳細な特徴を可能にします. このテクニックは,無形な活性医薬品成分 (API) を迅速に特定し,医薬品を変化させることなくAPIと補助剤の相互作用を明らかにします.
科学分野:
- 固体NMRスペクトロスコーピーは,固体NMRスペクトロスコーピーを用います.
- 薬学分析 薬学分析とは
- 材料の特徴付けについて
背景:
- 薬剤の配列を原子レベルで特徴づけることは,品質管理にとって極めて重要です.
- 伝統的なNMR方法では,サンプル変更が必要になるか,複雑な配方に対して感度が欠如する可能性があります.
- ダイナミック・ニュクレア・ポラライゼーション (DNP) は,固体状態のNMRに対する感度が向上しています.
研究 の 目的:
- DNP強化の固体NMRが,商用医薬品の配列を特徴づけるのに有用であることを実証する.
- 薬物製品内の原子レベルの構造と相互作用を分析する.
- 活性薬剤成分 (API) の物理的形状と粒子の大きさを決定する.
主な方法:
- 9.4TでのDNP強化の固体NMRスペクトロスコーピーを利用しました.
- 1,1,2,2-テトラクロロエタンでビラジカル分極剤を浸漬した軽く粉砕された錠剤.
- 105 Kで1次元と2次元13Cと15Nの固体NMRスペクトルを取得しました.
- 核スピン拡散をモデル化するために,極化時間の関数としてDNP強化 (ε) を分析した.
主要な成果:
- 4つの商用製剤でセチリジンジヒドロクロリドで40〜90のDNP強化 (ε) を達成しました.
- タブレット内のAPIの無形形を成功裏に特定しました.
- 1H-15N相関スペクトルを用いて直接のAPI-ポビドン相互作用を観察した.
- 微分分布モデリングを使用して0.07μm周辺の粒子半径を持つAPIドメインサイズを決定しました.
結論:
- DNP強化の固体NMRは,製薬剤の詳細な特徴づけのための強力な非破壊的な技術です.
- この方法は,高品質のスペクトルの迅速な取得を可能にし,微細構造情報を保存します.
- APIの物理的形状,粒子の大きさ,および薬物と補助剤の相互作用に関する洞察を提供します.
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