Formulation and Evaluation of Organogels Containing Hyaluronan Microparticles for Topical Delivery of Caffeine

AAPS PharmSciTech. 2018 Apr;19(3):1367-1376. doi: 10.1208/s12249-018-0955-x. Epub 2018 Jan 29.


Cellulite is a dermal disorder including the extracellular matrix, the lymphatic and microcirculatory systems and the adipose tissue. Caffeine is used as the active moiety depending its preventive effect on localization of fat in the cellular structure. Hyaluronic acid (hyaluronan-HA) is a natural constituent of skin that generates formation and poliferation of new cells having a remarkable moisturizing ability. The aim of this study is to formulate HA microparticles loaded with caffeine via spray-drying method. Resulting microparticle formulations (33.97 ± 0.3 μm, span < 2, 88.56 ± 0.42% encapsulation efficiency) were distributed in lecithin organogels to maintain the proper viscosity for topical application. Following the characterization and cell culture studies, in vitro drug release and ex vivo permeation studies were performed. The accumulated amount of caffeine was twice higher than the aqueous solution for the microparticle-loaded organogels at 24 h (8262,673 μg/cm2versus 4676,691 μg/cm2). It was related to the sustained behaviour of caffeine release from the microparticles. As a result, lecithin organogel containing HA-encapsulated microparticles could be considered as suitable candidate formulations for efficient topical drug delivery system of caffeine. In addition to that, synergistic effect of this combination appears as a promising approach for long-acting treatment of cellulite.

Keywords: caffeine; cellulite; hyaluronan microparticles; organogel; skin permeation.

MeSH terms

  • Administration, Topical
  • Animals
  • Caffeine / administration & dosage*
  • Caffeine / chemical synthesis
  • Caffeine / metabolism*
  • Drug Compounding
  • Drug Delivery Systems / methods*
  • Drug Liberation / physiology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gels / chemistry
  • Humans
  • Hyaluronic Acid / administration & dosage*
  • Hyaluronic Acid / chemical synthesis
  • Hyaluronic Acid / metabolism*
  • Microcirculation / drug effects
  • Microcirculation / physiology
  • Microspheres*
  • Rats
  • Skin Absorption / drug effects
  • Skin Absorption / physiology
  • Viscosity


  • Gels
  • Caffeine
  • Hyaluronic Acid