Why does a hydrophilic drug permeate skin, although it is not soluble in white petrolatum?
BACKGROUND
White petrolatum is broadly used as an ointment vehicle, although hydrophilic drugs cannot be easily dissolved in the vehicle.


METHODS
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 increased from the 'preapplied ointment' compared with the 'original ointment'. In addition, much higher skin permeation was also obtained using the 'preapplied ointment'. Separately, cholesteryl oleate, cholesterol, and ceramides were found in the 'preapplied white petrolatum'.


CONCLUSIONS
Thus, these endogenous lipids on the skin surface may enhance the release and skin permeation of FYK-1388b from white petrolatum ointment.
Ishii
Hiroshi
H
Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
Todo
Hiroaki
H
Terao
Akira
A
Hasegawa
Tetuya
T
Akimoto
Masayuki
M
Oshima
Kouichi
K
Sugibayashi
Kenji
K
D000287:Administration, Topical; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006146:Guanidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry; D008297:Male; D015394:Molecular Structure; D009823:Ointment Bases / Q000737:chemistry*; D009824:Ointments; D010577:Petrolatum / Q000737:chemistry*; D051381:Rats; D054772:Rats, Hairless; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility
C476604:FYK 1388; D006146:Guanidines; D006877:Hydroxamic Acids; D008055:Lipids; D009823:Ointment Bases; D009824:Ointments; D010577:Petrolatum