Stability and Formulation of Erlotinib in Skin Creams

Molecules. 2022 Feb 5;27(3):1070. doi: 10.3390/molecules27031070.

Abstract

Recent studies have highlighted the benefit of repurposing oral erlotinib (ERL) treatment in some rare skin diseases such as Olmsted syndrome. The use of a topical ERL skin treatment instead of the currently available ERL tablets may be appealing to treat skin disorders while reducing adverse systemic effects and exposure. A method to prepare 0.2% ERL cream, without resorting to a pure active pharmaceutical ingredient, was developed and the formulation was optimized to improve ERL stability over time. Erlotinib extraction from tablets was incomplete with Transcutol, whereas dimethyl sulfoxide (DMSO) allowed 100% erlotinib recovery. During preliminary studies, ERL was shown to be sensitive to oxidation and acidic pH in solution and when added to selected creams (i.e., Excipial, Nourivan Antiox, Pentravan, and Versatile). The results also showed that use of DMSO (5% v/w), neutral pH, as well as a topical agent containing antioxidant substances (Nourivan Antiox) were key factors to maintain the initial erlotinib concentration. The proposed ERL cream formulation at neutral pH contains a homogeneous amount of ERL and is stable for at least 42 days at room temperature in Nourivan cream with antioxidant properties.

Keywords: Olmsted; dermatology; drug repurposing; erlotinib; rare disease; skin cancer; stability indicating; topical.

MeSH terms

  • Antioxidants / chemistry*
  • Chromatography, High Pressure Liquid
  • Dimethyl Sulfoxide / chemistry
  • Drug Compounding
  • Drug Stability
  • Erlotinib Hydrochloride / chemical synthesis*
  • Erlotinib Hydrochloride / chemistry
  • Ethylene Glycols / chemistry
  • Hydrogen-Ion Concentration
  • Skin Cream / chemical synthesis*
  • Skin Cream / chemistry
  • Tablets

Substances

  • Antioxidants
  • Ethylene Glycols
  • Tablets
  • carbitol
  • Erlotinib Hydrochloride
  • Dimethyl Sulfoxide