Enhanced stability and reduced irritation of 4-n-butylresorcinol via nanoemulsion formulation: Implications for skin pigmentation treatment.

4-n-butylresorcinol (4-nBR) is a valuable ingredient to lighten skin and reduce pigmentation, contributing to an even skin tone and a more youthful appearance. However, its poor solubility, low stability, and strong irritation to the skin limit its application. In this study, 4-nBR was prepared into 4-n-butylresorcinol nanoemulsion (4-nBR-NE) for the first time, enhancing the solubility and stability of 4-nBR while greatly reducing its skin irritation. The relationship between the viscosity of nanoemulsion and the formulation process, as well as the impact of surfactant ratio on the formability of 4-nBR-NE were further studied. This led to the successful development of a nanoemulsion with adjustable viscosity (AV-NE) and with a low surfactant content. The particle size of 4-nBR-NE was 13.34 ± 0.16 nm with a PDI of 0.0853 ± 0.0191, indicating a uniform particle size distribution. The encapsulation rate of 4-nBR-NE was determined to be 80.05 ± 0.75 % via UV-Vis spectrophotometry. In addition, 4-nBR-NE demonstrated excellent stability over several months, with negligible changes in particle size. Cellular and transdermal evaluations confirmed that the preparation of 4-nBR-NE effectively reduced the original irritation cause by 4-nBR on cells and skin. Then, 4-nBR-NE was incorporated into an essence. This advancement enhances the applicability of 4-nBR in treating pigmentation disorders such as melasma and freckles, thereby increasing its applicability in pharmaceutical and cosmetic industries.