Physicochemical characteristics and ex vivo skin permeability for three phosphodiesterase 5 inhibitors (sildenafil, tadalafil and vardenafil): A proof-of-concept study for topical penile therapy

Abstract

Efficient topical drug delivery for phosphodiesterase inhibitors (PDE inhibitors) as a potential alternative to the oral therapy could revolutionize the treatment strategy of erectile dysfunction for decades to come. This work aims at investigating three selected members of PDE 5 inhibitors for potential topical penile therapy through studying preformulation characteristics such as pH solubility, partition coefficient, chemical stability and ex vivo permeation. Results showed that the three drugs showed pH-dependent solubility and lipid solubility (log P). Sildenafil showed the least solubility:dose ratio and least lipid solubility, compared to both vardenafil and tadalafil. The roles of two solubilizing agents and penetration enhancers (Solulan C24 and Pluronic F127) were studied. Pluronic F127 seemed to be superior and significantly enhanced skin permeability of sildenafil by 1.7. The apparent permeability coefficient (Papp) for the three drugs (silda, varda and tada) was 14, 76 and 90 cm/h, respectively. The forced degradation studies indicated that the three drugs were highly sensitive to both acid- and base-forced degradation; nevertheless, they are chemically stable against oxidative and photolytic degradations. In conclusion, topical penile therapy for tada and varda seems to more viable options than silda as far as skin permeation and solubility/dose ratio are concerned.