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

The effects of different concentrations of beta -cyclodextrin (beta -Cyd), hydroxypropyl-beta -cyclodextrin (HP-beta -CyD) and 2,6-di-O-methyl-beta -c yclodextrin (DM-beta -CyD) on percutaneous absorption of papaverine hydroch loride (PAY) were investigated. Abdominal rat skin mounted in Franz cells w as used for in vitro experiments. To evaluate CyD interaction with a bilaye r structure model, dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and DPPC- Chol (8:2 mole ratio) vesicles were used. CyD vesicle interaction was evalu ated by differential scanning calorimetry. Permeation through rat skin and calorimetric experiments demonstrated that at low concentrations DM-beta -C yD shows higher enhancer activity as a possible result of a perturbing acti on on the skin by a complexation of its lipid components, but at higher con centrations HP-beta -CyD is the most effective. By considering that HP-beta -CyD presents a very moderate destabilizing action on the skin, we conclud e that a 10% aqueous solution of this macrocycle appears to be the most sui table transdermal absorption enhancer for PAP.