Preparation, characterization and relative bioavailability of oral elemene o/w microemulsion

Int J Nanomedicine. 2010 Sep 7:5:567-72. doi: 10.2147/ijn.s12485.

Abstract

The objective was to develop an elemene oil/water (o/w) microemulsion and evaluate its characteristics and oral relative bioavailability in rats. Elemene was used as the oil phase and drug, polysorbate 80 as a surfactant along with ethanol, propylene glycol, and glycerol as the cosurfactants. The microemulsion was prepared by mixing method, or ultrasonication method in an ultrasonic bath. Its three-dimensional response surface diagram was drawn by Mathcad software. The microemulsion was characterized by visual observation, cross-polarized microscopy, size, zeta potential, acidity, viscosity, and surface tension measurement. The drug content and entrapment efficiency were determined by ultra fast liquid chromatography (UFLC) and liquid surface method. Blood was drawn from rats at different time points after oral administration of an elemene microemulsion or a commercial elemene emulsion for measurement of the drug in plasma by UFLC to establish the pharmacokinetic parameters and relative bioavailability. The elemene microemulsion as a clarified and isotropic system containing 1% elemene (w/v), 5% ethanol (v/v), 15% propylene glycol (v/v), 15% glycerol (v/v), and 5% polysorbate 80 (w/v), was characterized as (57.7 ± 2.8) nm in size, 0.485 ± 0.032 in polydispersity index, (3.2 ± 0.4) mv in zeta potential, (5.19 ± 0.08) in pH, 6 mpa·s in viscosity, (31.8 ± 0.3) mN·m(-1) in surface tension, (8.273 ± 0.018) mg·mL(-1) in content of β-elemene, and (99.81 ± 0.24)% in average entrapment efficiency. The area under the concentration-time curves from 0 h to 24 h (AUC(0→24h)) of the elemene microemulsion and commercial elemene emulsion were integrated to be 3.092 mg·h·L(-1) and 1.896 mg·h·L(-1) respectively, yielding a relative bioavailability of 163.1%. The present study demonstrates the elemene microemulsion as a new formulation with ease of preparation, high entrapment efficiency, excellent clarity, good stability, and improved bioavailability.

Keywords: elemene; microemulsion; relative bioavailability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Chemistry, Pharmaceutical
  • Drug Stability
  • Emulsions
  • Female
  • Male
  • Oils
  • Particle Size
  • Polysorbates
  • Rats
  • Rats, Sprague-Dawley
  • Sesquiterpenes / administration & dosage*
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacokinetics*
  • Solubility
  • Surface-Active Agents
  • Water

Substances

  • Emulsions
  • Oils
  • Polysorbates
  • Sesquiterpenes
  • Surface-Active Agents
  • Water
  • elemene