固体35Cl NMRの適用は,塩化水素製薬およびそのポリモルフの構造的特徴化に用いられる
Hiyam Hamaed1, Jenna M Pawlowski, Benjamin F T Cooper
1Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada N9B 3P4.
Journal of the American Chemical Society
|July 29, 2008
まとめ
固体 (35) Cl NMRスペクトロスコピーは,HCl製薬の構造とポリモルフィズムを効果的に探査します. この技術は,異なる結晶形の素早い識別と構造的解釈を提供し,医薬品の開発を支援しています.
科学分野:
- 固体NMRスペクトロスコーピー 固体NMRスペクトロスコーピー
- 医薬品科学 医薬品科学とは
- クリスタルグラフィーです.
背景:
- 塩酸塩 (HCl) は,知られている製薬用塩の約50%を占めています.
- ポリモルフィズムを理解することは,薬剤の有効性および安全性にとって極めて重要です.
- 固体 (35) Cl NMR (SSNMR) スペクトロスコピーは,これらの化合物を特徴付けるための潜在的な方法を提供します.
研究 の 目的:
- HCl製薬の構造とポリモルフィズムを分析するための (35) Cl SSNMRスペクトロスコピーの有用性を評価する.
- SSNMRのパラメータを結晶学データと計算結果と相関させる.
- ポリモルフの識別のための指紋採取技術として (35) Cl SSNMRの応用を実証する.
主な方法:
- 高磁場 (21.1 T) で (35) Cl マジックアングルスピニング (MAS) SSNMRスペクトルの取得.
- 変化する磁場 (9.4 と 21.1 T) の静止サンプルの記録スペクトル.
- 単結晶と粉末のX線 difraktionを用いて,補完的な分析のためのab initio計算とともに.
主要な成果:
- (35) SSNMRのClスペクトルは,微妙な環境変化に対する感受性を明らかにし,これは電場グラデーション (EFG) と化学シフト (CS) パラメータに反映されています.
- SSNMRの粉末パターンは,ポリモルフを識別するための迅速な指紋として機能しました.
- 実験 (35) Cl EFGとCSテンソールパラメータは,第一原理計算と良好な一致を示した.
結論:
- (35) Cl SSNMRスペクトロスコピーは,HCl製薬の構造解釈とポリモルフ識別のための貴重なツールです.
- このテクニックの感度と初期モデリングの精度は,医薬品のポリモルフスクリーニングにおける広範な適用の有望性を示しています.
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