1-monooleoyl-rac-glycerol and isopropyl-myristate

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.

Topics: Administration, Cutaneous; Animals; Animals, Newborn; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Carriers; Drug Stability; Emulsions; Ethylene Glycols; Glycerides; Hexoses; Kinetics; Models, Chemical; Myristates; Oils; Oleic Acid; Oleic Acids; Organic Chemicals; Permeability; Polysorbates; Silymarin; Skin; Skin Absorption; Solubility; Surface-Active Agents; Swine; Technology, Pharmaceutical

Cutaneous delivery of combinations of antioxidants offers the possibility of enhanced protection against UV-radiation. In this study, we investigated the potential of sugar-based microemulsions containing monoglycerides to promote simultaneous cutaneous delivery of lycopene and ascorbic acid, and increase tissue antioxidant activity. Lycopene and ascorbic acid were incorporated (0.04% and 0.2% (w/w), respectively) in decylglucoside-based microemulsions containing isopropyl myristate mixed with monocaprylin (ME-MC), monolaurin (ME-ML) or monoolein (ME-MO) as oil phase. The microemulsions increased lycopene delivery into porcine ear skin by 3.3- to 8-fold compared to a drug solution. The effect of microemulsions on ascorbic acid cutaneous delivery was more modest (1.5-3-fold), and associated with an approximately 2-fold increase in transdermal delivery. According to their penetration-enhancing ability, the microemulsions were ranked ME-MC>ME-MO>ME-ML. This superiority of ME-MC coincided with a stronger effect in decreasing skin electrical resistance. After 18 h of treatment, the viability of bioengineered skin treated with ME-MC was 2.2-times higher compared to Triton-X100 (moderate irritant), demonstrating that ME-MC is less cytotoxic. Skin treatment with ME-MC containing both antioxidants increased the tissue antioxidant activity by 10.2-fold, but no synergism between the antioxidants was observed.

Topics: Administration, Cutaneous; Animals; Antioxidants; Ascorbic Acid; Caprylates; Carotenoids; Drug Delivery Systems; Emulsions; Excipients; Glucosides; Glycerides; Laurates; Lycopene; Monoglycerides; Myristates; Skin; Skin Absorption; Swine