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  • Title: Vasomodulation influences on the transdermal delivery of Ibuprofen.
    Author: Carter SG, Zhu Z, Varadi G, Veves A, Riviere JE.
    Journal: J Pharm Sci; 2013 Nov; 102(11):4072-8. PubMed ID: 23996466.
    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.
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