Formulation of Silymarin Microemulsion for dermal delivery

Abstract

Silymarin is a standardized extract from the seeds of Silybum marianum. Due to its antioxidant, anti-inflammatory, and immunomodulatory properties, silymarin may prevent UV-induced skin disorders including erythema, edema, sun burn cell formation, photoaging, and skin cancer. The objective of this study is to prepare silymarin-loaded microemulsions for dermal delivery and then evaluate its release properties, stabilities and permeability. Glyceryl monooleate, oleic acid, ethyl oleate, isopropyl myristate were selected as an oil phase, mixture of Tween 20® and HCO-40® (1:1), Labrasol® and HCO-40® (1:1) or Span 20® and HCO-40® (1:1) were selected as surfactants, and Transcutol® was used as a cosurfactant to construct the pseudo-ternary phase diagrams. From each pseudo-ternary phase diagram, o/w microemulsion with low surfactants/cosurfactant mixture (Smix) content was selected for dermal delivery of silymarin and to avoid skin irritation from surfactant and oil. Microemulsions containing 2% w/w silymarin showed a good physical stability; remained transparent and no phase separation or drug precipitation after 6 heating-cooling cycles. However, silybin, the main active component of silymarin, degraded during storage of microemulsions at 40C for 6 months. The percentages of silybin remainings were sequenced in the order of surfactants: Labrasol® > Tween 20® > Span 20® (as HCO-40® was used in every formulation). In vitro releases of silymarin microemulsions showed the prolong release when compared to its solution (40% ethanol in phosphate buffer saline pH 7.4). All silymarin release profiles showed the best fit with Higuchi kinetics and the release rate constants of silymarin from microemulsions were not significantly different. In vitro skin permeation study found that silybin could not be detected in the concentrated receiver fluid. The percentages of silybin remainings in skin extracts from silymarin microemulsions were not significantly different, except for the solution which significantly higher than microemulsions. However, alcohol solutions are still not suitable for skin delivery due to their skin irritation. For further studies, the permeation study in occlusive condition should be performed comparing to this non-occlusive condition, as well as in vivo studies of efficacy and skin irritation of silymarin microemulsions.