Glyceryl Monooleyl Ether-Based Liquid Crystalline Nanoparticles as a Transdermal Delivery System of Flurbiprofen: Characterization and <i>in Vitro</i> Transport

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  • Uchino Tomonobu
    Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka Laboratory of Clinical Pharmacokinetics, Shizuoka General Hospital
  • Murata Akiko
    Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka
  • Miyazaki Yasunori
    Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka Laboratory of Clinical Pharmacokinetics, Shizuoka General Hospital
  • Oka Toshihiko
    Department of Physics, Graduate School of Science, Shizuoka University Nanomaterials Research Division, Research Institute of Electronics, Shizuoka University
  • Kagawa Yoshiyuki
    Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka Laboratory of Clinical Pharmacokinetics, Shizuoka General Hospital

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  • Glyceryl Monooleyl Ether-Based Liquid Crystalline Nanoparticles as a Transdermal Delivery System of Flurbiprofen : Characterization and in Vitro Transport

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Abstract

Liquid crystalline nanoparticles (LCNs) were prepared using glyceryl monooleyl ether (GME) by the modified film rehydration method. Hydrogenated lecithin (HL), 1,3-butylene glycol (1,3-BG), and Poloxamer 407 were used as additives. The prepared LCN formulations were evaluated based on particle size, small-angle X-ray diffraction (SAXS) analysis, 1H- and 19F-NMR spectra, and in vitro skin permeation across Yucatan micropig skin. The composition (weight percent) of the LCN formulations were GME–HL–1,3-BG (4 : 1 : 15), 4% GME-based LCN and GME–HL–1,3-BG (8 : 1 : 15), 8% GME-based LCN and their mean particle sizes were 130–175 nm. Flurbiprofen 5 and 10 mg was loaded into 4% GME-based LCN and 8% GME-based LCN systems, respectively. The results of SAXS and NMR suggested that both flurbiprofen-loaded formulations consist of particles with reverse type hexagonal phase (formation of hexosome) and flurbiprofen molecules were localized in the lipid domain through interaction of flurbiprofen with the lipid components. Flurbiprofen transport from the LCN systems across the Yucatan micropig skin was increased compared to flurbiprofen in citric buffer (pH=3.0). The 8% GME-based LCN systems was superior to the 4% GME-based LCN for flurbiprofen transport. Since the internal hexagonal phase in the 8% GME-based LCN systems had a higher degree of order compared to the 4% GME-based LCN in SAXS patterns, the 8% GME-based LCN system had a larger surface area, which might influence flurbiprofen permeation. These results indicated that the GME-based LCN system is effective in improving the skin permeation of flurbiprofen across the skin.

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