ポリモルフの安定性に対する表面溶解と構造の影響を理解する:機械化学と理論的アプローチの組み合わせ
Ana M Belenguer1, Giulio I Lampronti1,2, Nicola De Mitri1
1Department of Chemistry , University of Cambridge , Lensfield Road , Cambridge CB2 1EW , U.K.
Journal of the American Chemical Society
|October 30, 2018
まとめ
溶媒の濃度は,ボールミルでのコクリスタルポリモルフの安定性を影響する. 異なる溶媒とそれらの濃度は,表面溶解効果に関連した多形的な結果を決定する.
科学分野:
- 固体化学
- クリスタルグラフィー
- 材料科学
背景:
- ポリモルフィズムがコクリスタルの特性や性能に大きく影響する.
- 多形変異の制御は 医薬品開発に不可欠です
- 液体補助研磨 (LAG) はコクリスタル合成と改変のための機械化学の経路を提供します.
研究 の 目的:
- テオフィリン・ベンザミド共結晶の熱力学的安定性に対する溶媒濃度の影響を調査する.
- 表面溶媒の溶解現象とポリモルフィックな行動を相関させる.
- ボールミルのLAGでポリモルフ均衡を達成するための実験条件を確立する.
主な方法:
- ボールミルの液体補助研磨 (LAG) で 16 種類の溶媒を使用しています.
- ポリモルフの濃度と結晶の大きさを監視するためのEx-situ粉末X線 difraktion (PXRD).
- サーフェスト・サイト・インタラクション・ポイント (SSIP) とソルベーション・エネルギーの計算のためのSSIMPLE方法.
主要な成果:
- 溶媒濃度の関数として16の均衡ポリモルフ濃度曲線を実験的に決定した.
- ポリモルフィック相互変換における協同性を示す均衡曲線の溶媒依存変異を証明した.
- ポリモルフ表面の特定された露出機能群 (フォームIのテオフィリンπ系面,フォームIIのNメチル群)
- 均衡状態の結晶体サイズにおける溶媒特異の観測
結論:
- ボールミルのLAGは,溶媒の種類と濃度に敏感な結果でコクリスタルポリモルフ均衡を達成できます.
- 表面溶解は,LAG条件下でコクリスタルポリモルフの熱力学的安定性を決定する上で重要な役割を果たします.
- 発見は,機械化学的方法と溶媒の選択を通じてコクリスタルポリモルフィズムを制御するための洞察を提供します.
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