Natural polymer-stabilized multiple water-in-oil-in-water emulsions: a novel dermal drug delivery system for 5-fluorouracil

J Pharm Pharmacol. 2014 May;66(5):658-67. doi: 10.1111/jphp.12194. Epub 2013 Dec 23.

Abstract

Objectives: The aim of this study was to create multiple water-in-oil-in-water (W/O/W) emulsions with an increased long-term stability as skin delivery systems for the hydrophilic model drug 5-fluorouracil.

Methods: Multiple W/O/W emulsions were prepared in a one-step emulsification process, and were characterized regarding particle size, microstructure and viscosity. In-vitro studies on porcine skin with Franz-type diffusion cells, tape stripping experiments and attenuated total reflectance-fourier transform infrared spectroscopy (ATR-FTIR) were performed.

Key findings: The addition of Solagum AX, a natural polymer mixture of acacia and xanthan gum, led to multiple W/O/W emulsions with a remarkably increased long-term stability in comparison to formulations without a thickener. The higher skin diffusion of 5-fluorouracil from the multiple emulsions compared with an O/W-macroemulsion could be explained by ATR-FTIR. Shifts to higher wave numbers and increase of peak areas of the asymmetric and symmetric CH2 stretching vibrations confirmed a transition of parts of the skin lipids from an ordered to a disordered state after impregnation of porcine skin with the multiple emulsions.

Conclusions: Solagum AX is highly suitable for stabilization of the created multiple emulsions. Moreover, these formulations showed superiority over a simple O/W-macroemulsion regarding skin permeation and penetration of 5-fluorouracil.

Keywords: 5-fluorouracil; ATR-FTIR; multiple emulsions; optical light microscopy; skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acacia*
  • Administration, Cutaneous
  • Animals
  • Drug Delivery Systems*
  • Drug Stability
  • Emulsions* / chemistry
  • Fluorouracil / administration & dosage*
  • Hydrophobic and Hydrophilic Interactions
  • Lipids
  • Oils
  • Particle Size
  • Polymers* / chemistry
  • Polysaccharides, Bacterial*
  • Skin / metabolism*
  • Spectroscopy, Fourier Transform Infrared
  • Swine
  • Viscosity
  • Water

Substances

  • Emulsions
  • Lipids
  • Oils
  • Polymers
  • Polysaccharides, Bacterial
  • Water
  • xanthan gum
  • Fluorouracil