Competing Role of Water in Inclusion of Indomethacin and Volatile Organic Compounds by Native Cyclodextrins

The hydration was found to reduce an efficiency of drug encapsulation by native cyclodextrins (CDs) when water is added above a certain threshold level. The hydration water competes with indomethacin for solid-phase inclusion in gamma-cyclodextrin (gamma CD) and beta-cyclodextrin (beta CD) with an increase of water contents to the saturation level. No compe ting effect was observed for alpha-cyclodextrin (alpha CD) with this drug. The hydration effect for indomethacin correlates with the influence of hydration water on inclusion of volatile organic guests by native CDs. For these guests and gamma CD, the competing hydration effect was estimated also by determination of vapor sorption isotherms and was found higher than that for beta CD but in most cases lower than such effect for alpha CD. The inclusion affinity and capacity of dried gamma CD for water and organic guests were determined and a significant size exclusio n effect was observed, which contributes to the water-guest competition. The ratio between competing and activation roles of water for the studied three native cyclodextrins correlates with the parameters of their unit cells in hydrates and in dried state.