Inclusion complex formation of captopril with α- and β-cyclodextrins in aqueous solution: NMR spectroscopic and molecular dynamic studies.

Ikeda, Yoichi; Motoune, Sohko; Matsuoka, Toshikazu; Arima, Hidetoshi; Hirayama, Fumitoshi; Uekama, Kaneto.

Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., Hiroshima, Japan. Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto, Japan.

Abstract

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 aq. soln. was studied by 1H- and 13C-NMR spectroscopies, including ROESY and GROESY techniques, by kinetic methods and by mol. dynamic calcns. The oxidative degrdn. of captopril was markedly suppressed in α-CyD solns., whereas β-CyD and HP-β-CyD had negligible stabilizing effects. These NMR and kinetic results suggested that α-CyD includes preferably the Pr thioalc. moiety of captopril, depositing the proline moiety outside the cavity. On the other hand, β-CyD includes a whole mol. 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 mol. dynamic studies.