title: Vasomodulation influences on the transdermal delivery of Ibuprofen.
abstract: The purpose of the study was to evaluate the effect of adding peripheral vasodilators, tolazoline, or papaverine, to transdermal drug delivery vehicles with the goal of improving the tissue bioavailability of transdermally delivered ibuprofen. Ibuprofen (150 mg) formulations with several concentrations of two different vasodilators and/or a penetration enhancer (PE) complex were topically applied to rabbits. Plasma levels of ibuprofen were determined by a validated high-performance liquid chromatography method and evaluated at 0, 0.5, 1, 2, and 3 h. The PE complex enhanced the plasma ibuprofen level approximately sevenfold versus control, and tolazoline (0.005%) added to the PE complex increased the plasma levels of ibuprofen approximately another twofold compared with the PE. Higher concentrations of tolazoline paradoxically did not exhibit vasodilator enhancement to ibuprofen delivery. Papaverine was tested in the same manner. In this set of experiments, PE increased the plasma ibuprofen 3.7-fold versus control, and addition of papaverine (0.0005%) increased plasma ibuprofen an additional 3.3-fold compared with the PE formulation. Transdermal formulations of ibuprofen containing low concentrations of tolazoline or papaverine increased plasma ibuprofen levels in the presence of passive PE components.
authors.affiliation: BioChemics, Inc, Danvers, Massachusetts, 01923.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Carter
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhu
authors.forename: Gyula
authors.initials: G
authors.lastname: Varadi
authors.forename: Aristidis
authors.initials: A
authors.lastname: Veves
authors.forename: Jim E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007052:Ibuprofen / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D010208:Papaverine / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D011817:Rabbits; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D014043:Tolazoline / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014665:Vasodilator Agents; D014043:Tolazoline; D010208:Papaverine; D007052:Ibuprofen
keywords: blood flow; formulation vehicle; ibuprofen; permeation enhancer; pharmacokinetics; skin; transdermal delivery; vasodilation