Inclusion Complex Formation of Captopril with α‐ and β‐Cyclodextrins in Aqueous Solution: NMR Spectroscopic and Molecular Dynamic Studies
| Autor: | Hidetoshi Arima, Sohko Motoune, Yoichi Ikeda, Fumitoshi Hirayama, Kaneto Uekama, Toshikazu Matsuoka |
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| Rok vydání: | 2002 |
| Předmět: |
chemistry.chemical_classification
Cyclodextrins alpha-Cyclodextrins Captopril Magnetic Resonance Spectroscopy Aqueous solution Cyclodextrin Stereochemistry Carboxylic acid beta-Cyclodextrins Water Pharmaceutical Science Inclusion compound Pharmaceutical Solutions chemistry.chemical_compound chemistry Polymer chemistry Thiol medicine Moiety Molecule medicine.drug |
| Zdroj: | Journal of Pharmaceutical Sciences. 91:2390-2398 |
| ISSN: | 0022-3549 |
| DOI: | 10.1002/jps.10232 |
| Popis: | The inclusion complex formation of α‐cyclodextrin (α‐CyD), β‐cyclodextrin (β‐CyD), and 2‐hydroxylpropyl‐β‐cyclodextrin (HP‐β‐CyD) with an angiotensin converting enzyme inhibitor, captopril, in aqueous solution was studied by 1H‐ and 13C‐nuclear magnetic resonance spectroscopies, including ROESY and GROESY techniques, by kinetic methods and by molecular dynamic calculations. The oxidative degradation of captopril was markedly suppressed in α‐CyD solutions, whereas β‐CyD and HP‐β‐CyD had negligible stabilizing effects. These NMR and kinetic results suggested that α‐CyD includes preferably the propyl thioalcohol moiety of captopril, depositing the proline moiety outside the cavity. On the other hand, β‐CyD includes a whole molecule of captopril in the cavity, locating the carboxylic acid within the cavity and the terminal thiol moiety outside the cavity. These inclusion structures were supported by molecular dynamic studies. © 2002 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:2390–2398, 2002 |
| Databáze: | OpenAIRE |
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