title: Systemic enhancement of papaverine transdermal gel for erectile dysfunction.
abstract: To enhance the systemic transdermal delivery of papaverine for the treatment of erectile dysfunction, several factors that influence transdermal delivery of papaverine HCl were studied. The effects of membrane types for in vitro permeation study, human skin layers, solvent/cosolvent systems and the penetration enhancers on the transdermal permeation of papaverine HCl were investigated. A combination of caproic acid, ethanol and water in the volume ratio of 50%:30%:20% was chosen as penetration enhancer and incorporated in two gel bases: 18% Pluronic F-127 and 2% Carbopol 940. In vivo skin permeation studies were performed with two loading doses (0.6% and 2%) in rabbits. The flux and permeability coefficient of papaverine HCl through different human skin layers suggested that the major barrier layer for papaverine HCl was residing primarily in the stratum corneum. However, the viable epidermis and dermis layer also contributed certain degrees of diffusion resistance. Differential Scanning Calorimetry study showed that penetration enhancer exhibited a counter effect with papaverine HCl on the temperature and enthalpy in both gels. In vitro drug release study demonstrated significant increases in the steady-state flux, permeability coefficient and enhancement ratio in these gels. Faster drug transports and higher bioavailability were also observed in rabbits. Skin irritation test performed in rabbits demonstrated a mild skin reaction with mean PII scores of 2 and below; however the recovery was fast. In conclusion, caproic acid, ethanol and water in the volume ratio of 50%:30%:20% is an effective penetration enhancer to deliver papaverine HCl transdermally for systemic absorption.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy & Drug Manufacturing, Pharos University in Alexandria, Canal Mahmudaya, Smouha, Alexandria, Egypt. mingming.wen@pua.edu.eg
authors.forename: Ming Ming
authors.initials: MM
authors.lastname: Wen
authors.forename: Amal H
authors.initials: AH
authors.lastname: El-Kamel
authors.forename: Said A
authors.initials: SA
authors.lastname: Khalil
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000328:Adult; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002208:Caproates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004058:Diffusion; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000378:metabolism; D000431:Ethanol / Q000737:chemistry; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D010208:Papaverine / Q000008:administration & dosage* / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012997:Solvents; D013552:Swine; D014867:Water / Q000737:chemistry; D055815:Young Adult
chemical_list: D000180:Acrylic Resins; D002208:Caproates; D005782:Gels; D012997:Solvents; D014867:Water; D020442:Poloxamer; D000431:Ethanol; C006903:carbopol 940; D010208:Papaverine