Development of silymarin topical formulation: In vitro and ex vivo dermal kinetics of silymarin

Abstract

Silymarin constituents are extensively investigated in the treatment of skin disorders. The main constituents of silymarin include taxifolin (TX), silychristin (ST), silydianin (SDN), silybin A (SA), silybin B (SB), isosilybin A (ISA) and isosilybin B (ISB). The objective of the present study was to determine in-vitro dermal kinetics of individual silymarin constituents in human skin models and to develop a silymarin topical formulation. In-vitro studies indicate human skin binding of silymarin was in the range of 2.09 to 12.3% and half-life of silymarin constituents was > 15.5 h in epidermal and dermal cells. Topical silymarin cream was prepared using sulfobutylether-β-cyclodextrins as solubilizer and propylene glycol as permeation enhancer. The cream was subjected to ex-vivo human skin permeation studies. In ex-vivo studies, cumulative amount of TX, ST, SDN, SA, SB, ISA and ISB permeated across human cadaver skin at 24 h was 921 ± 13.5, 1992 ± 67.6, 345 ± 39.2, 1089 ± 45.0, 1770 ± 100, 1469 ± 81.5 and 1285 ± 33.1 ng/cm², respectively. The amount TX, ST, SDN, SA, SB, ISA and ISB retained after 24 h was 60.7 ± 8.2, 376 ± 45.5, 72.3 ± 6.9, 66.4 ± 8.0, 208 ± 31.3, 154 ± 12.4 and 102 ± 6.3 ng/mg of human cadaver skin, respectively. The study results demonstrate silymarin topical formulation could deliver significant amount of silymarin constituents into skin. The developed silymarin formulation could be beneficial for treatment or management of a broad spectrum of dermatological disorders.

Keywords: Dermal kinetics; Silymarin; Skin; Sulfobutylether-β-cyclodextrins; Topical formulation.