Thirteen buffers were investigated for their effect on the binding of adamantanol to β-cyclodextrin and hydroxypropyl-β-cyclodextrin . Stability constants for the β-cyclodextrin complex ranged from 14,800 to 46,000 M, and the binding enthalpies were between -23.2 and -10.4 kJ/mole . Compared to water, the stability constant in seven carboxylic acid buffers (citric acid, maleic acid, fumaric acid, succinic acid, malonic acid, malic acid and tartaric acid) was reduced . All seven buffers exhibited a competitive mechanism . Binding constants for the interaction between β-cyclodextrin and buffers ranged from 4 to 44 M, and binding enthalpies were in the range -19 to -11 kJ/mole . There was a relation between the chemical structures of the buffers and their ability to bind to cyclodextrin . All seven buffers had a carbon chain consisting of more than three carbons in the backbone . Hydroxyl groups on the carbon chain decreased the binding affinity . H and ROESY NMR spectroscopy supported inclusion of the citric acid into the cyclodextrin cavity, although the results for succinic and maleic acids were ambiguous . The results demonstrated that some buffers can interact with cyclodextrin complexes, and careful considerations are necessary when choosing a buffer for cyclodextrin research.