title: Why does a hydrophilic drug permeate skin, although it is not soluble in white petrolatum?
abstract: 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.
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Todo
authors.forename: Akira
authors.initials: A
authors.lastname: Terao
authors.forename: Tetuya
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Masayuki
authors.initials: M
authors.lastname: Akimoto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Oshima
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugibayashi
mesh_terms: 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
chemical_list: C476604:FYK 1388; D006146:Guanidines; D006877:Hydroxamic Acids; D008055:Lipids; D009823:Ointment Bases; D009824:Ointments; D010577:Petrolatum