In Vitro Evaluation of Sunscreen Safety: Effects of the Vehicle and Repeated Applications on Skin Permeation from Topical Formulations

Abstract

The evaluation of UV-filter in vitro percutaneous absorption allows the estimation of the systemic exposure dose (SED) and the margin of safety (MoS) of sunscreen products. As both the vehicle and pattern of application may affect sunscreen safety and efficacy, we evaluated in vitro release and skin permeation of two widely used UV-filters, octylmethoxycinnamate (OMC) and butylmethoxydibenzoylmethane (BMBM) from topical formulations with different features (oil in water (O/W) emulsions with different viscosity, water in oil (W/O) emulsion, oils with different lipophilicity). To mimic in-use conditions, we carried out experiments repeating sunscreen application on the skin surface for three consecutive days. BMBM release from all these vehicles was very low, thus leading to poor skin permeation. The vehicle composition significantly affected OMC release and skin permeation, and slight increases of OMC permeation were observed after repeated applications. From skin permeation data, SED and MoS values of BMBM and OMC were calculated for all the investigated formulations after a single application and repeated applications. While MoS values of BMBM were always well beyond the accepted safety limit, the safety of sunscreen formulations containing OMC may depend on the vehicle composition and the application pattern.

Use of Vegetable Oils to Improve the Sun Protection Factor of Sunscreen Formulations

“…As widely reported in the literature, vehicles can strongly affect the performance of cosmetic products, including sunscreen formulations [8,9,[21][22][23][24][25][26]. The effectiveness of sunscreens and their compliance with consumer expectations requires that the product be easily spread onto skin, leaving a thin, uniform, adhering, and water-resistant film on the cutaneous surface.…”

“…Recently, selected herbal oils have been investigated to develop sunscreen formulations with a reduced content of organic UV-filters while still maintaining a high sun protection factor (SPF) [4][5][6]. Indeed, the safety of organic UV-filters has been widely debated because some studies on the skin penetration and permeation of these molecules have reported that they are able to permeate the skin at sufficient rates to be recovered from systemic circulation [7][8][9]. Therefore, to address the safety issue of organic UV-filters, several researchers performed in vivo toxicity studies from which the margin of safety (MoS) was calculated by comparing the potential human systemic exposure with the no adverse effect level (NOAEL) [10,11].…”

Penetration Enhancement of Topical Formulations

“…However, we are reminded by Montenegro et al [13] that enhanced skin penetration may not always be a desirable outcome. When it comes to sunscreen safety, the aim is to limit skin penetration of chemicals from the topical formulations to avoid toxicity.…”

Topical Delivery of 3-O-ethyl l-ascorbic Acid from Complex Solvent Systems

“…Even though the ability of some solvents to promote delivery of EA across porcine skin in vitro has been confirmed, the permeability of the compound was comparatively low, with 0.6% to 7.5% of the applied dose delivered after 24 h. Additionally, commonly used excipients and/or penetration enhancers such as ethoxydiglycol, dipropylene glycol, 1,5 pentanediol, and tripropylene glycol did not promote permeation of EA through porcine skin [5]. Generally, it is accepted that skin permeation of actives is vehicle-dependent [7,8] and combinations of solvents have been shown to act synergistically to enhance permeation of compounds [9][10][11].…”