Emulsifier-induced changes to the human skin barrier – Connection to ceramide profiles and assessment as a skin lesion model

Emulsifiers are common excipients in dermal products stabilizing formulations such as creams and emulsions. But due to their potential for skin irritation, emulsifiers for pharmaceutical use should be tested regarding their tolerability before introducing them to the skin of patients. In this study, a systematic investigation with six oil in water (o/w)-emulsifiers was performed on the forearms of 12 healthy human volunteers, six female and six male. We analyzed the effects of pharmaceutical emulsifiers on the macroscopic skin health parameters measured as trans-epidermal water loss (TEWL) and skin hydration and measured the ceramide profile of the treated skin sites using liquid chromatography coupled to mass spectrometry (LC-MS) in order to assess the skin tolerability of the investigated emulsifiers. In a second step, a Partial Least Squares Regression was employed to investigate relationships between changes in the ceramide profile to changes in the TEWL of skin treated with a non-ionic as well as an anionic emulsifier. Skin health measurements showed that the applied emulsifiers inflicted no significant changes compared to the water-treated sample, demonstrating a remarkable skin tolerability. The employed regression model showed a good fit as well as adequate prediction and identified ceramide species associated with impaired skin barrier function. Furthermore, it was found that the relationship between the ceramide profile and the skin barrier function in emulsifier-induced skin damage shows distinct similarities to the interplay of ceramides and skin barrier function in lesional skin linked to Atopic Dermatitis (AD), hinting towards a common underlying mechanism and opening up possibilities to simulate disease-related changes to the skin for the development of skin damage models. In conclusion, these detailed investigations yield insight into possible mechanisms of emulsifier induced skin damage and show its versatility in the investigation of pharmaceutical emulsifiers for formulation development as well as basic research.