Why does a hydrophilic drug permeate skin, although it is not soluble in white petrolatum?
GROUND: White petrolatum is broadly used as an ointment vehicle, although hydrophilic drugs cannot be easily dissolved in the vehicle. METHOD: The aim of this study was to evaluate the release and skin permeation profiles of a model hydrophilic agent, N1-[2-(4-guanidinophenyl)-1(S)-(N-methylcarbamoyl)ethyl]-N4-hydroxy-2(R)-iso-butyl-3(S)-(3-phenylpropyl)succinamide hydrochloride (FYK-1388b), from the ointment. RESULTS: The release rate of FYK-1388b was very low; however, high skin permeation and skin content of the drug were found. We supposed that this was due to endogenous lipids or sebum, because white petrolatum had a high affinity to these lipids. To evaluate the effect of lipids on the enhanced release and skin permeation of FYK-1388b, ‘preapplied white petrolatum’ was made by applying the drug-free white petrolatum on the hairless rat skin for 6 hours. Then the drug ointment was prepared using the ‘preapplied white petrolatum’. The release rate of FYK-1388b was markedly increase
