Solvent effects on chemical processes. 10. Solubility of alpha-cyclodextrin in binary aqueous-organic solvents: relationship to solid phase composition.

The equilibrium solubility at 25 degrees C of alpha-cyclodextrin was measured in several binary aqueous-organic solvent mixtures, the organic cosolvents being methanol, 2-propanol, ethylene glycol, and acetone. Solubility maxima were observed as the solvent composition was varied from pure water to pure cosolvent. The maximum in methanol systems was hardly detectable, but it was very pronounced in 2-propanol and acetone, and two maxima were seen in the ethylene glycol system. Karl Fischer analysis of the solid phase isolated from 2-propanol/water equilibrium systems showed that alpha-cyclodextrin hexahydrate is the stable form in water, whereas a solid phase containing three water molecules per molecule of alpha-cyclodextrin is the stable form in the presence of 2-propanol. The appearance of a solubility maximum in this system, and by extension presumably in the other cosolvent systems, is attributed to the existence of more than one stable solid phase of alpha-cyclodextrin.