title: Improvement of effect of water-in-oil microemulsion as an oral delivery system for fexofenadine: in vitro and in vivo studies.
abstract: Fexofenadine (FEX) has high solubility and low permeability (BCS, Class III). In this work, novel FEX loaded water in oil microemulsion (w/o) was designed to improve bioavailability and compared with Fexofen(®) syrup in in vitro and in vivo studies. In addition, pharmacokinetic parameters in permeability studies were estimated by using WinNonLin software program. w/o microemulsion system was optimized using a pseudoternary phase diagram, composed of span 80/lutrol F 68 (9.5:0.5 w/w), oleic acide, isopropyl alcohol and water as surfactant mixture; oil and cosurfactant was developed for oral drug delivery. w/o microemulsion systems were characterized by phase behavior, particle size, viscosity and solubilization capacity. In vitro studies were studied using Caco-2 cell monolayer. Pharmacokinetic parameters of w/o microemulsion were investigated in rabbits and compared to Fexofen(®) syrup. Fexofen(®) syrup and microemulsion were administered by oral gavage at 6 mg/kg of the same concentration. The experimental results indicated that microemulsion (HLB = 5.53) formed nanometer sized droplets (33.29 ± 1.76) and had good physical stability. This microemulsion increased the oral bioavailability of FEX which was highly water-soluble but fairly impermeable. The relative bioavailability of FEX microemulsion was about 376.76% compared with commercial syrup in rabbits. In vitro experiments were further employed for the enhanced effect of the microemulsion for FEX. These results suggest that novel w/o microemulsion plays an important role in enhancing oral bioavailability of low permeability drugs.
authors: Faculty of Pharmacy, Department of Biopharmaceutics and Pharmacokinetics, Ege University, Izmir, Turkey. evren.gundogdu@ege.edu.tr
authors: E
authors: E
authors: Gundogdu
authors: I Gonzalez
authors: IG
authors: Alvarez
authors: E
authors: E
authors: Karasulu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D018938:Caco-2 Cells; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D019301:Oleic Acid / Q000737:chemistry; D010539:Permeability; D011817:Rabbits; D012995:Solubility; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; D014867:Water; D019301:Oleic Acid; D016593:Terfenadine; C093230:fexofenadine