Ultrasound-mediated topical delivery of econazole nitrate with potential for treating Raynaud's phenomenon

Int J Pharm. 2020 Apr 30;580:119229. doi: 10.1016/j.ijpharm.2020.119229. Epub 2020 Mar 14.


The study aims to assess the ultrasound-assisted econazole nitrate (EN) permeation from topically applied formulations with potential for treating Raynaud's phenomenon. Optimization of ultrasound parameters such as the distance of the horn, application time and amplitude were performed. In vitro percutaneous absorption studies were performed using econazole formulations (F2_HPMC dispersion, F4_Lipoderm® Activemax™ Cream) across the ultrasound-treated porcine skin and were compared with the control group (skin samples without ultrasound). Histology and ATR-FTIR studies were performed on treated skin samples. A constant frequency (20 kHz) ultrasound application with 40% amplitude, 0.5 cm distance between ultrasound horn and the skin surface for 2 min was optimized. The permeation of EN was found to be higher from ultrasound-treated skin samples than the control group. Drug permeation from F2_HPMC dispersion was found to be higher as compared to the other formulations and the marketed EN cream. Histological evaluation confirmed that F2_HPMC dispersion showed no signs of toxicity. ATR-FTIR studies revealed a slight increase in the CH2 stretching vibrations (~2920 cm-1 and 2850 cm-1) in ultrasound-treated skin samples as compared with the control. In conclusion, the ultrasound-assisted transdermal delivery of F2_HPMC dispersion could be further studied as a new therapy for Raynaud's phenomenon.

Keywords: Cold exposure; Econazole nitrate; Flux; HPMC; Lag-time; Permeation; Raynaud’s phenomenon; TRPM-8; Topical; Ultrasound.

MeSH terms

  • Administration, Cutaneous
  • Animals
  • Antifungal Agents / administration & dosage
  • Chemistry, Pharmaceutical / methods
  • Econazole / administration & dosage*
  • Permeability
  • Raynaud Disease / drug therapy*
  • Skin / metabolism
  • Skin Absorption / physiology
  • Swine


  • Antifungal Agents
  • Econazole