Formulation of microemulsion systems for dermal delivery of silymarin.

AAPS PharmSciTech (2012-02-22)
Vipaporn Panapisal, Sawitree Charoensri, Angkana Tantituvanont
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Diethylene glycol monoethyl ether, ReagentPlus®, 99%
Sigma-Aldrich
Isopropyl myristate, 98%
Sigma-Aldrich
Span® 20
Sigma-Aldrich
Isopropyl myristate, ≥98%
Sigma-Aldrich
Di(ethylene glycol) ethyl ether, ≥99%
Sigma-Aldrich
Isopropyl myristate, ≥90% (GC)
Sigma-Aldrich
Ethyl oleate, 98%
Supelco
Isopropyl myristate, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Ethyl oleate, tested according to Ph. Eur.
Sigma-Aldrich
Ethyl oleate, natural, ≥85%
Glycerol mono-oleate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Ethyl oleate, technical grade, 70%