The use of preservatives in topical formulations is essential to prevent microbial growth in water-containing vehicles like creams, gels, and lotions. Ethanol (EtOH) is a common preservative known for its antimicrobial properties and solvent capabilities. However, ethanol’s impact on skin barrier function and its potential to alter the dermal penetration of active compounds raises concerns. This study investigates whether using ethanol as a preservative in topical creams affects the penetration efficacy of active ingredients in both healthy and barrier-disrupted skin.
Methods:
The study used a hydrophilic (sodium fluorescein) and a lipophilic (Nile red) fluorescent dye as active ingredient surrogates. These dyes were incorporated into creams with and without 20% v/v ethanol. The dermal penetration efficacy was assessed via epifluorescence microscopy on ex vivo porcine ear skin, both intact and irritated with acetone. Transepidermal water loss (TEWL) and skin hydration were measured to evaluate biophysical skin properties.
Key Findings and Discussion:
• Formulation Characteristics: The addition of ethanol decreased the mean particle size of the cream from approximately 20 µm to 2 µm, but it also decreased the physical stability of the cream.
• Dermal Penetration on Intact Skin: Ethanol reduced the dermal penetration of both hydrophilic (by about 40%) and lipophilic (by about 20%) surrogates on intact skin. This was unexpected, as ethanol is generally known as a penetration enhancer.
• Dermal Penetration on Irritated Skin: Ethanol had minimal impact on the penetration of the hydrophilic surrogate in irritated skin, with a slight (15%) decrease in the penetration of the lipophilic surrogate.
• Bio-Physical Skin Properties: On intact skin, ethanol increased TEWL and decreased skin hydration. Conversely, on irritated skin, ethanol decreased TEWL and increased skin hydration.
•”Pudding Skin” Hypothesis: The study proposes the formation of a “Pudding skin” layer in the early stages of skin impairment. This is a thin layer of dried skin that “seals” the lower parts, reducing dermal penetration and water loss.
This research highlights the complex role of ethanol in topical formulations. Contrary to its reputation as a penetration enhancer, ethanol, when used as a preservative, can reduce the dermal penetration of active compounds, especially in intact skin. The study introduces the novel “Pudding skin” hypothesis, suggesting that impaired skin undergoes different stages of barrier disruption that affect penetration efficacy. Future research should focus on the viscoelasticity of the skin to provide a more holistic understanding of the proposed hypothesis. Understanding these dynamics is crucial for tailoring formulations to specific skin conditions, optimizing therapeutic outcomes, and carefully balancing the benefits of preservatives with their potential impact on active ingredient delivery.
Link to the study: https://www.mdpi.com/1999-4923/17/2/196
