Enhancement of propranolol hydrochloride and diazepam skin absorption in vitro: effect of enhancer lipophilicity.

摘要: The enhancement of model hydrophilic (propranolol hydrochloride) and lipophilic (diazepam) drug penetration across rat hairless mouse skin in vitro has been studied. Preliminary experiments established that most n-alkanes having chain lengths between 7 16 promote the flux both drugs. For propranolol, varied parabolically with carbon number; for diazepam, heptane was ineffective all others were essentially equipotent. Enhancement by n-nonane then compared n-nonanol. Propranolol increased enhancers, whereas diazepam not affected less alcohol. propranolol n-nonanol examined as a function adjuvant concentration applied formulation. Maximum increases maximum rates 6.5-fold (n-nonane) 8.2-fold (n-nonanol) determined. As expected, saturable, indicative maximally perturbed stratum corneum. Finally, enhancing abilities six monoterpenes assessed. purely hydrocarbon analogues promoted transport to an extent similar n-nonane. terpenes hydrogen-bonding ability, however, only enhanced (at level comparable n-nonanol). While data reported do directly reveal mechanistic information on percutaneous enhancement, they provide starting point rational investigation interrelationships drug, enhancer, skin. Such is clearly essential optimization exploitation transdermal delivery.