アセトアミノフェンの反復的な高通量ポリモルフィズム研究と,フォームIIIのための実験的に派生された構造
Matthew L Peterson1, Sherry L Morissette, Chris McNulty
1TransForm Pharmaceuticals, Inc., 610 Lincoln Street, Waltham, Massachusetts 02451, USA.
Journal of the American Chemical Society
|September 13, 2002
まとめ
新しい高通量結晶化プラットフォームであるCrystalMaxは,3つのアセトアミノフェンの結晶形態の準備と特徴付けを可能にしました. 入手が難しい第3形態の構造モデルが提案され,その困難な準備が説明されました.
科学分野:
- 結晶化科学とは,結晶化に関する科学です.
- マテリアルサイエンス 材料科学
- 医薬品科学とは,医薬品科学のことである.
背景:
- アセトアミノフェンはポリモルフィズムを示しており,知られている結晶形は3つあります.
- 特定のポリモルフの特徴づけと準備は困難である.
- 高通量メソッドは,効率的なポリモルフスクリーニングの可能性を秘めています.
研究 の 目的:
- アセトアミノフェンポリモルフ製剤のための高通量結晶化プラットフォームを開発し,利用する.
- アセトアミノフェンの3つの既知の結晶形態を特徴づけるために.
- 難解な第三のアセトアミノフェンの結晶形の構造を解明するために.
主な方法:
- 高通量結晶化プラットフォーム (CrystalMax) の開発は,設計ソフトウェア,ロボットハンドリング,およびマイクロ分析を統合しています.
- 様々な超飽和駆動方法を用いた並列結晶化実験.
- 構造の解明のための粉末X線 difraktion (PXRD) 分析.
- 構造仮説の生成のための計算モデリング.
主要な成果:
- クリスタルマックスを用いてアセトアミノフェンの3つの結晶の形状の準備と特徴づけに成功しました.
- PXRDのデータは,第3のアセトアミノフェンポリモルフの構造に関する洞察を提供した.
- O-H...O(H) 水素結合によって安定化される第3形態の2層構造モデルを提案した.
- 提案された構造は,溶液からこの形を得ることの難しさを説明するのに役立ちます.
結論:
- CrystalMaxプラットフォームは,高通量ポリモルフのスクリーニングと準備に有効です.
- この研究は,アセトアミノフェンの第3形態である挑戦的なアセトアミノフェンの構造的な洞察を提供します.
- 結晶構造と製剤方法の理解は,医薬品開発に不可欠です.
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