Drug/cyclodextrin: beyond inclusion complexation

Development of cyclodextrins as enabling excipients began decades ago and during this time a conventional view of the substrate?Ccyclodextrin interaction was formed that has persisted in spite of numerous contradicting observations. Here the shortcomings of the phase-solubility method are elucidated. The limited permeability of drug/cyclodextrin complexes through semi-permeable membrane, as well as osmometric data and images from transition electronic microscopy (TEM) are used as convincing evidences of aggregation of cyclodextrins and their complexes. The necessity of updating the existing notions of cyclodextrin complexation is discussed.