title: Utility of nano-sized, water-in-oil emulsion as a sustained release formulation of glycyrrhizin.
abstract: The aim of this study was to determine the efficiency of nano-sized water-in-oil (w/o) emulsions that encapsulate glycyrrhizin (GZ) (Rp-I) as a sustained release formulation for subcutaneous administration. Four formulations were assessed in rats for 8-72 h: nano-sized water-in-oil (w/o) emulsion encapsulating GZ (Rp-I), GZ aqueous solution (Rp-II), oil-in-water (o/w) emulsion containing GZ (Rp-III), and w/o emulsion containing solid GZ (Rp-IV). All had a GZ concentration of 150 mg/ml. Over an 8-h period, GZ elimination in bile after subcutaneous administration of Rp-I, Rp-II, Rp-III, and Rp-IV (50 mg/kg GZ) was 10.8%, 97.0%, 81.0%, and 7.1%, respectively. The elimination of GZ into bile after the administration of Rp-IV was the lowest (30.5%) at the 72-h endpoint, dropping significantly from 48 to 72 h. On the other hand, the elimination rate of GZ after the administration of Rp-I was sustained at a constant level (1.8-2.1 mg/24 h) over 72 h. GZ concentration in liver at 72 h in Rp-I was highest (19.9 µg/g tissue) among the four formulations, suggesting that the release of GZ from the Rp-I formulation is constant, at least up to 72 h after administration. These results suggest that a nano-sized w/o emulsion is useful as a sustained release formulation for long-term therapy of chronic hepatitis.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University. k-koga@hokuriku-u.ac.jp
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Koga
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nishimon
authors.forename: Hisashi
authors.initials: H
authors.lastname: Ueta
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Matsuno
authors.forename: Kanji
authors.initials: K
authors.lastname: Takada
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism; D003692:Delayed-Action Preparations; D004655:Emulsions; D006035:Glycyrrhiza / Q000737:chemistry; D019695:Glycyrrhizic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006521:Hepatitis, Chronic / Q000188:drug therapy; D008099:Liver / Q000378:metabolism; D008297:Male; D053758:Nanoparticles; D009821:Oils; D010936:Plant Extracts / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014867:Water
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D009821:Oils; D010936:Plant Extracts; D014867:Water; D019695:Glycyrrhizic Acid