Theoretical and experimental investigations on miconazole/cyclodextrin/acid complexes: Molecular modeling studies
- 作者：Valé ; ry Barillaro ; Georges Dive ; Pascal Bertholet ; Brigitte Evrard ; Luc Delattre ; Zié ; mons Eric ; Geraldine Piel
- 关键词：Miconazole ; Cyclodextrins ; Molecular modeling ; Complex structure ; Multicomponent complex ; AM1 calculations ; Supercritical carbon dioxide
- 刊名：International Journal of Pharmaceutics
- 出版年：2007
- 期刊代码：24_03785173
- 类别：pha
- 出版时间：5 September 2007
- 卷：342
- 期：1-2
- 页码：152-160
- 文件大小：712 K
摘要
The inclusion of miconazole into cyclodextrin cavity has been demonstrated by different authors. Preliminary studies have shown which fragment of the molecule is involved in the inclusion. In the present study, AM1 approximate molecular orbital calculations have been performed on several cyclodextrins complexes (βCD, HPβCD and HPγCD) with miconazole and acidic compounds (maleic, fumaric and L-tartaric acids) as partners. For all the binary complexes, the inclusion of the dichlorobenzene–CH2–O-group leads to the most stable complex. For the ternary complexes, depending on their conformation and/or their structures, the acids can either stabilize or destabilize the complex. All the theoretical results were in good agreement with experimental data of miconazole inclusion yields into cyclodextrins. This work clearly demonstrates that the structure of both cyclodextrin and acid plays a key-role in the formation of inclusion complexes.