title: 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.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. Vipaporn.P@chula.ac.th
authors.forename: Vipaporn
authors.initials: V
authors.lastname: Panapisal
authors.forename: Sawitree
authors.initials: S
authors.lastname: Charoensri
authors.forename: Angkana
authors.initials: A
authors.lastname: Tantituvanont
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000831:Animals, Newborn; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004355:Drug Stability; D004655:Emulsions; D005026:Ethylene Glycols / Q000737:chemistry; D005989:Glycerides / Q000737:chemistry; D006601:Hexoses / Q000737:chemistry; D007700:Kinetics; D008956:Models, Chemical; D009226:Myristates / Q000737:chemistry; D009821:Oils / Q000737:chemistry*; D019301:Oleic Acid / Q000737:chemistry; D009829:Oleic Acids / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry; D010539:Permeability; D011136:Polysorbates / Q000737:chemistry; D012838:Silymarin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013552:Swine; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D005026:Ethylene Glycols; D005989:Glycerides; D006601:Hexoses; D009226:Myristates; D009821:Oils; D009829:Oleic Acids; D009930:Organic Chemicals; D011136:Polysorbates; D012838:Silymarin; D013501:Surface-Active Agents; C440220:Labrasol; C008205:isopropyl myristate; D019301:Oleic Acid; C014822:sorbitan monolaurate; C010111:carbitol; C005953:monoolein; C033180:ethyl oleate