Formulation optimization, skin irritation, and efficacy characterization of a novel skin-lightening agent.

Skin-lightening preparations are used by people all over the world for a diverse range of dermatologic indications. The gold standard treatment for skin lightening is with hydroquinone but has been controversial because of the presence of several side effects. Therefore, there has been a constant search for developing new treatment alternatives. Furthermore, the new amendments and bans on animal testing by ECVAM have made the three-dimensional models like EpiDerm(™) and MelanoDerm(™) increasingly popular. This work aims at the formulation development for a new skin-lightening agent, SMA-012, followed by testing for skin irritation and efficacy. Formulation parameters such as concentration of SMA-012, amount of ethanol, effect of permeation enhancers and pH were first optimized using Franz cell experiments. Tape stripping and underlying skin assays were performed to analyze the amounts of SMA-012 in different layers of skin. The irritation potential and efficacy of the screened formulation were evaluated using Epiderm(™) and Melanoderm(™) models. Skin permeation experiments suggested that concentrations of 0.1% SMA-012, 35% ethanol, and pH of 8.5 to be the best formulation characteristics. This particular formulation was found to be nonirritant for short-term exposure, when tested in Epiderm(™) model and also significantly effective in decreasing the amount of melanin in pigmented skin equivalent models. SMA-012 shows a good promise as a skin-lightening agent for cosmetic and therapeutic applications. Additionally, our study demonstrates the application of skin equivalent models as alternatives to animal testing in studying the regulation of skin pigmentation.