Formulation of Drug-Cyclodextrin Complexes

Abstract

Cyclodextrins are water-soluble oligosaccharides that form hydrophilic complexes with many lipophilic poorly soluble drugs. Cyclodextrins and cyclodextrin complexes do not permeate intact skin, and, thus, hydrophilic cyclodextrins do not affect the skin barrier, stratum corneum. Studies have shown that, in general, cyclodextrins only enhance drug permeation into and through the skin from aqueous vehicles and only if an aqueous diffusion barrier at the skin exterior contributes to the overall skin permeation barrier. Cyclodextrins do not enhance drug penetration from lipophilic vehicles or when the skin barrier itself is the main permeation barrier. Cyclodextrins are able to prevent drug partition from an aqueous exterior into the skin. Thus, it is of uttermost importance to optimize composition of cyclodextrin-containing drug vehicles with regard to drug release and permeation. In this chapter, the effects of cyclodextrins on percutaneous drug permeation are described. Simple mathematical models are used to explain how and when cyclodextrins act as penetration enhancers and then how these models can be applied to optimize drug delivery from a topical formulation.