Self-assembly of cyclodextrins: the effect of the guest molecule

Abstract

The principle action by which cyclodextrins solubilize compounds is via inclusion complex formation. However, data suggest that cyclodextrins and their complexes also aggregate in solution and this aggregation contributes to their ability to solubilize poorly water-soluble materials. The current effort aims at better understanding the role of guest molecule nature (i.e. its structural and functional peculiarities) in cyclodextrin complex aggregation as well as in the aggregate stability assessed using a cellophane membrane permeability assay. A test set of 11 acidic, basic and neutral drugs and antibacterial agents (i.e. guests) were examined with regard to their interaction with hydroxypropyl-β-cyclodextrin (HPβCD) and the resulting ability of the formed aggregates to move through a semi-permeable membrane of various molecular weight cut-off values. The data suggested that the interaction of HPβCD with certain guests resulted in the formation of structure large enough to poorly penetrate semi-permeable membrane. The aggregates appeared to be highly dynamic in that there were no qualitative differences between systems that were diluted immediately prior to permeation experiments and those allowed to equilibrate. Pharmaceutical polymers which have been shown to enhance solubilizing efficiency of cyclodextrins had little or no effect on the stability of the aggregates using the permeability paradigm as an endpoint with the exception of carboxymethylcellulose.