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-cyclodextrin (DM-beta-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-beta-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-beta-CyD is the most effective. By considering that HP-beta-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.
Ventura
C A
CA
Dipartimento Farmaco-Chimico, Università di Messina, Italy.
Fresta
M
M
Paolino
D
D
Pedotti
S
S
Corsaro
A
A
Puglisi
G
G
D000005:Abdomen; D000279:Administration, Cutaneous; D000818:Animals; D002942:Circular Dichroism; D003505:Cyclodextrins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D003956:Dialysis; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008297:Male; D008567:Membranes, Artificial; D008954:Models, Biological; D010208:Papaverine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D010539:Permeability / Q000187:drug effects; D051381:Rats; D012869:Skin Absorption / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics
D003505:Cyclodextrins; D004337:Drug Carriers; D008567:Membranes, Artificial; D014665:Vasodilator Agents; D010208:Papaverine