Design of a Topically Applied Gel Spray Formulation with Ivermectin Using a Novel Low Molecular Weight Gelling Agent, Palmitoyl-Glycine-Histidine, to Treat Scabies

Chem Pharm Bull (Tokyo). 2018;66(3):327-333. doi: 10.1248/cpb.c17-00965.

Abstract

Palmitoyl-glycine-histidine (Pal-GH) is a new low molecular weight gelling agent. It exhibits thixotropic behavior, low viscosity, and high dissolving properties for a wide range of hydrophilic to lipophilic drugs. Orally administered ivermectin (IVM) is used to treat scabies. However, this treatment is associated with well-known side effects, thus a study is awaited to search for alternative routes of administration. Although a topical formulation of IVM could be a candidate, it requires whole body application except the head and face for several hours on a daily basis. Therefore, in this study, we prepared a gel spray formulation containing IVM as an approach for application to large skin areas with a single spray application without further contact with the applied formulation. Pal-GH gel spray formulations were prepared from its aqueous solution by a heating and cooling method. Rheological behavior and physical appearance (spraying, spreading ability, volume of spraying, and homogeneity) of the prepared formulations were evaluated. Pal-GH gel with propylene glycol demonstrated impressive rheological properties (typical thixotropic behavior) with high hysteresis area among all the tested Pal-GH gels and spreading ability. The obtained IVM concentration in the skin after topical application of 0.1% IVM-containing Pal-GH formulation onto hairless rats was much higher than the reported therapeutic concentration obtained from oral administration in humans. These results suggested that topical application of IVM using a Pal-GH gel spray formulation could be an alternative to the conventional oral forms for the scabies treatment.

Keywords: gel spray formulation; ivermectin; low-molecular weight gelling agent; skin concentration; thixotrophy.

MeSH terms

  • Administration, Topical
  • Animals
  • Chromatography, High Pressure Liquid
  • Drug Compounding
  • Drug Design
  • Gels / chemistry*
  • Ivermectin / chemistry*
  • Ivermectin / pharmacology
  • Ivermectin / therapeutic use
  • Molecular Weight
  • Rats
  • Rats, Hairless
  • Rheology
  • Scabies / drug therapy
  • Skin / chemistry
  • Skin / drug effects
  • Skin / metabolism
  • Spectroscopy, Fourier Transform Infrared

Substances

  • Gels
  • Ivermectin