Glabridin nanosuspension for enhanced skin penetration: formulation optimization, in vitro and in vivo evaluation

Glabridin, a polyphenolic flavonoid from licorice, has inspired great interest for its antioxidant, anti-inflammatory and skin-lightening activities. However, low water solubility and poor stability of glabridin impedes its topical application in cosmetic products and therapies of dermal diseases. The purpose of this study was to develop a nanosuspension formulation of glabridin to improve its skin permeation. Glabridin nanosuspensions were prepared using anti-solvent precipitation-homogenization method, and Box-Behnken design was adopted to investigate the effects of crucial formulation variables on particle size and to optimize the nanosuspension formulation. The optimal formulation consisted of 0.25% glabridin, 0.47% Poloxamer 188 and 0.11% Polyvinylpyrrolidone K30, and the obtained nanosuspension showed an average particle size of 149.2 nm with a polydispersity index of 0.254. Furthermore, the nanosuspension exhibited significantly enhanced drug permeation flux of glabridin through rat skin with no lag phase both in vitro and in vivo, compared to the coarse suspension and physical mixture. The glabridin nanosuspension showed no significant particle aggregates and a drug loss of 5.46% after storage for 3 months at room temperature. With its enhanced skin penetration, the nanosuspension might be a more preferable formulation for topical administration of poorly soluble glabridin.