Formulation evaluation of ketoconazole microemulsion-loaded hydrogel with nigella oil as a penetration enhancer

J Cosmet Dermatol. 2019 Dec;18(6):1742-1750. doi: 10.1111/jocd.12945. Epub 2019 Apr 13.


Background: Onychomycosis is an opportunistic fungal infection often infecting people with compromised immune system. Currently available treatment interventions such as physical, surgical, and chemical-based approaches are successful in treating the condition, however, are painful and nonpatient complaint. Moreover, dermal creams with antifungal agents do not penetrate nail plate as required; hence, there is a necessity of developing a novel formulation with enhanced penetration.

Aims: The aim of the present research work was to develop ketoconazole microemulsion-loaded hydrogel formulation containing nigella oil as permeation enhancer for the treatment of onychomycosis.

Methods: Screening of oils, surfactants, and cosurfactants were done based on solubility studies followed by the construction of pseudo-ternary phase diagrams with 2% ketoconazole. The microemulsion was characterized for globule size, zeta potential, viscosity, and thermodynamic stability. Ex-vivo studies were carried out using Franz diffusion cells using porcine skin membrane. The antifungal activity of microemulsion-loaded hydrogel was evaluated using cup plate method using Candida albicans and Aspergillus niger.

Results: The optimized microemulsion had a composition of 54.97% Capryol:Nigella (2:1), 36.07% Transcutol:Propylene glycol (2:1), and 7.13% water and was later incorporated into polymeric gel base. The microemulsion-loaded hydrogel exhibited a 10 hours sustained release profile as compared to the marketed cream and an enhanced activity against marketed ketoconazole cream and compared with marketed ketoconazole formulation.

Conclusion: The thermodynamic stability, sustained drug release with greater permeation, and enhanced activity due to the presence of nigella oil in microemulsion-loaded hydrogel warrant its application as an excellent vehicle for treating fungal infections.

Keywords: antifungal; microemulsion-loaded hydrogel; nigella oil; onychomycosis; penetration enhancers; synergistic activity.

MeSH terms

  • Administration, Topical
  • Animals
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / pharmacokinetics
  • Aspergillus niger / drug effects
  • Candida albicans / drug effects
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacokinetics
  • Disease Models, Animal
  • Drug Liberation
  • Emulsions
  • Humans
  • Hydrogels / chemistry
  • Ketoconazole / administration & dosage*
  • Ketoconazole / pharmacokinetics
  • Microbial Sensitivity Tests
  • Nails / drug effects
  • Nails / metabolism
  • Nigella / chemistry
  • Onychomycosis / drug therapy*
  • Onychomycosis / microbiology
  • Permeability / drug effects
  • Pharmaceutical Vehicles / chemistry
  • Pharmaceutical Vehicles / pharmacology*
  • Plant Oils / pharmacology*
  • Seeds / chemistry
  • Skin / drug effects
  • Skin / metabolism
  • Swine


  • Antifungal Agents
  • Delayed-Action Preparations
  • Emulsions
  • Hydrogels
  • Pharmaceutical Vehicles
  • Plant Oils
  • Ketoconazole