Transdermal delivery of flurbiprofen from surfactant-based vesicles: particle characterization and the effect of water on in vitro transport.
Flurbiprofen loaded rigid and elastic vesicles comprising the bilayer-forming surfactant sucrose-ester laurate were prepared by the film rehydration and extrusion method. The charge-inducing agent sodium dodecyl sulfate, and the micelle-forming surfactants, sorbitan monolaurate, polyethylene glycol monolaurate, and polysorbate 20, were used to enhance elasticity. Vesicle formulations were evaluated for size, zeta potential, (1)H and (19)F nuclear magnetic resonance (NMR) spectra, and in vitro skin permeation across Yucatan micropig (YMP) skin. Vesicle formulations were stable for 2 weeks and their mean sizes were 95-135 nm. NMR spectroscopy showed that flurbiprofen molecular mobility was restricted by interaction with vesicle components because of entrapment in vesicle bilayers. Moreover, sorbitan monolaurate-containing vesicles strongly retained flurbiprofen molecules. After non-occlusive application to YMP skin, flurbiprofen transport from all vesicle formulations was superior to that of flurbiprofen alone and remarkably decreased after water vaporization. Polarization microscopy and small-angle X-ray diffraction analysis showed that the vesicle formulation was transferred to liquid crystalline state. Suppression of vesicle transition to the liquid crystalline state was observed with applications of both large quantities and diluted samples. The presence of water in the formulations was associated with maintenance of the vesicle structure and greater flurbiprofen transport across YMP skin.
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan; Laboratory of Clinical Pharmacokinetics, Shizuoka General Hospital, 4-27-1 Kita-ando, Aoi-ku, Shizuoka 420-8527, Japan. Electronic address: uchinot@u-shizuoka-ken.ac.jp.
Tomonobu
T
Uchino
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Yuiko
Y
Matsumoto
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
Akiko
A
Murata
Department of Physics, Graduate School of Science, Shizuoka University, 836 Oya, Suruga-ku, Shizuoka 422-8529, Japan.
Toshihiko
T
Oka
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan; Laboratory of Clinical Pharmacokinetics, Shizuoka General Hospital, 4-27-1 Kita-ando, Aoi-ku, Shizuoka 420-8527, Japan.
Yasunori
Y
Miyazaki
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan; Laboratory of Clinical Pharmacokinetics, Shizuoka General Hospital, 4-27-1 Kita-ando, Aoi-ku, Shizuoka 420-8527, Japan.
Yoshiyuki
Y
Kagawa
D000279:Administration, Cutaneous; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D005480:Flurbiprofen / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D009924:Organ Culture Techniques; D012869:Skin Absorption / Q000187:drug effects* / Q000502:physiology; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D014867:Water / Q000737:chemistry* / Q000378:metabolism
D004337:Drug Carriers; D013501:Surface-Active Agents; D014867:Water; D005480:Flurbiprofen
(1)H NMR; (19)F NMR; Flurbiprofen; Liquid crystal; Skin permeation; Surfactant-based vesicle