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Formulation of Microemulsion Systems for Dermal Delivery of Silymarin

Abstract

Silymarin is a standardized extract from Silybum marianum seeds, known for its many skin benefits such as antioxidant, anti-inflammatory, and immunomodulatory properties. In this study, the potential of several microemulsion formulations for dermal delivery of silymarin was evaluated. The pseudo-ternary phase diagrams were constructed for the various microemulsion formulations which were prepared using glyceryl monooleate, oleic acid, ethyl oleate, or isopropyl myristate as the oily phase; a mixture of Tween 20®, Labrasol®, or Span 20® with HCO-40® (1:1 ratio) as surfactants; and Transcutol® as a cosurfactant. Oil-in-water microemulsions were selected to incorporate 2% w/w silymarin. After six heating–cooling cycles, physical appearances of all microemulsions were unchanged and no drug precipitation occurred. Chemical stability studies showed that microemulsion containing Labrasol® and isopropyl myristate stored at 40°C for 6 months showed the highest silybin remaining among others. The silybin remainings depended on the type of surfactant and were sequenced in the order of: Labrasol® > Tween 20® > Span 20®. In vitro release studies showed prolonged release for microemulsions when compared to silymarin solution. All release profiles showed the best fits with Higuchi kinetics. Non-occlusive in vitro skin permeation studies showed absence of transdermal delivery of silybin. The percentages of silybin in skin extracts were not significantly different among the different formulations (p > 0.05). Nevertheless, some silybin was detected in the receiver fluid when performing occlusive experiments. Microemulsions containing Labrasol® also were found to enhance silymarin solubility. Other drug delivery systems with occlusive effect could be further developed for dermal delivery of silymarin.

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Acknowledgments

The authors would like to thank Chulalongkorn University Graduate Research Fund for partially financing this study. We also acknowledge Associate Professor Dr. Iman Saad Ahmed, College of Pharmacy, University of Sharjah, United Arab Emirates for her scientific review; Berlin Pharmaceutical Co., Ltd. (Thailand) for supplying silymarin; Croda Co., Ltd. (Thailand) for supplying glyceryl monooleate and ethyl oleate; and Kru Somboon farm (Ratchaburi, Thailand) for supplying the dead newborn pigs.

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Correspondence to Vipaporn Panapisal.

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Panapisal, V., Charoensri, S. & Tantituvanont, A. Formulation of Microemulsion Systems for Dermal Delivery of Silymarin. AAPS PharmSciTech 13, 389–399 (2012). https://doi.org/10.1208/s12249-012-9762-y

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  • DOI: https://doi.org/10.1208/s12249-012-9762-y

Key words

  • dermal delivery
  • microemulsion
  • silybin
  • silymarin