Biomembrane model interaction and percutaneous absorption of papaverine through rat skin: Effects of cyclodextrins as penetration enhancers

The effects of different concentrations of β-cyclodextrin (β-CyD), hydroxypropyl-β-cyclodextrin (HP-β-CyD) and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CyD) on percutaneous absorption of papaverine hydrochloride (PAP) were investigated. Abdominal rat skin mounted in Franz cells was used for in vitro experiments. To evaluate CyD interaction with a bilayer structure model, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and DPPC-Chol (8:2 mole ratio) vesicles were used. CyD vesicle interaction was evaluated by differential scanning calorimetry. Permeation through rat skin and calorimetric experiments demonstrated that at low concentrations DM-β-CyD shows higher enhancer activity as a possible result of a perturbing action on the skin by a complexation of its lipid components, but at higher concentrations HP-β-CyD is the most effective. By considering that HP-β-CyD presents a very moderate destabilizing action on the skin, we conclude that a 10% aqueous solution of this macrocycle appears to be the most suitable transdermal absorption enhancer for PAP.