Effect of γ-cyclodextrin on the in vitro skin permeation of a steroidal drug from nanoemulsions: Impact of experimental setup

Numerous reports on the enhancement effect of cyclodextrins (CDs) on the skin permeation of dermally applied drugs exist, the majority of which is based on in vitro diffusion cell studies. The specific experimental setup of such studies may skew the obtained results, which is rarely discussed in the context of CD studies. Thus, the aim of this work was to conduct a systematic in vitro investigation of the permeation enhancement potential of γ-CD on a steroidal drug from a nanoemulsion. The role of critical diffusion cell parameters such as the dose of application, occlusive conditions, the nature of the receptor medium and the skin thickness were investigated. The results showed that significantly enhanced skin permeation rates of fludrocortisone acetate were indeed caused by 1% (w/w) of γ-CD at both finite and infinite dose conditions. At 0.5% (w/w) of γ-CD, significant enhancement was only achieved at infinite dose application. Additional in vitro tape stripping experiments confirmed these tendencies, but the observed effects did not reach statistical significance. It may be concluded that the full permeation enhancement potential of the CD as observed in the franz-cell setup can only be realised at infinite dose conditions while preserving the formulation structure.