Antioxidants are a prominent feature in cosmetics due to the research showing their ability to quench free radicals. Antioxidants however are notoriously unstable and deteriorate. Despite interesting scientific research, topical preparations have often been disappointing for several reasons. Most preparations are very unstable on exposure to light and air. Oxidation occurs very rapidly, and once oxidized these preparations are useless. Even when products are stable, many of them do not penetrate the stratum corneum.
Some consumers believe that because of this instability that there is no benefit from using antioxidants at all because as soon as they are exposed to air and light they degrade. This belief could not be further from the truth as chemists have developed new ways to address these issues.
Ways in which the stability of antioxidants has been addressed are as follows:
- Modification of Vitamins and new derivatives.
Ascorbic acid derivatives
Chemical modification of ascorbic acid has led to more stable derivatives such as ascorbyl esters with fatty acids or ascorbyl phosphate salts.
Alkyl esters of ascorbic acid
One of the most studied lipophilic esters is ascorbyl palmitate, which is often used in cosmetic and food preparations as an alternative source of ascorbic acid. It can penetrate into the skin more easily when compared with the acidic form. Although it is often acknowledged as more stable, its stability is still not adequate. The main problem is oxidation. Studies have indicated that Ascorbyl Palmitate’s chemical stability depends on the structural properties of the topical preparation used.
Among the formulations, colloidal lipid carriers such as nanoemulsions, microemulsions, nanosuspensions, liposomes, solid lipid nanoparticles (SLNs) and oil-loaded SLNs have been studied extensively. The importance of carrier type and structure for Ascorbyl Palmitate is critical for protection against degradation.
Ascorbyl Palmitate has been found to be most stable in solid lipid nanoparticles and non-hydrogenated phospholipid liposomes. Ascorbyl Palmitate also requires high concentrations to reduce degradation.
Ascorbyl phosphate salts
Ascorbyl phosphate salts (sodium, magnesium) are hydrophilic derivatives of ascorbic acid. According to current research they are among the most stable ascorbic acid derivatives.
A preliminary study on SAP stability in microemulsions endorsed its use in cosmetic and pharmaceutical preparations because > 95% of non-degraded compound remained after 2 months.
SAP liposomes enhance antioxidant penetration through the stratum corneum in deeper layers of the skin when compared with an aqueous solution.
Vitamin E derivatives
In the case of vitamin E, the acetate and acid succinate esters are commonly used for their high stability.
A great deal of effort is being put into designing and synthesizing new derivatives of vitamin E. One of them, d-tocopherol glucoside, has demonstrated improved stability and skin capability to metabolize the prodrug to active form (i.e., d-tocepherol) when compared with the acetate form.
New drug delivery systems
For useful topical application of antioxidants several obstacles must be overcome. Delivery systems help antioxidants to reach the site of action, rather than altering their chemical nature or biological activity. New drug delivery systems can be applied to improve the solubility, permeability and stability of antioxidants.
Special attention is given to microemulsions because they make simultaneous skin delivery of both vitamins possible.
Microemulsions are clear, heat stable dispersions composed of water, oil and surfactants. Their specific structure gives them considerable potential to act as drug delivery vehicles by incorporating lipophilic, hydrophilic and/or amphiphilic drugs. They have been shown to increase drug solubility, increase rate and extent of absorption, modify drug release, protect labile drugs, reduce patient variability, mask unpleasant odor and significantly increase bioavailability compared with classical dosage forms such as emulsions, gels and solutions. The formation of micro-emulsions as well as most of their advantages arises from the relatively high surfactant concentration required. As surfactants are possible irritants, it is crucial to select mild, biocompatible and non-irritant compounds.
Liposomes are defined as structures consisting of one or more concentric spheres of lipid bilayers separated by water. Liposomes are predominantly formed by phospholipids. Their advantages are based on the similarity of vesicle bilayer structure to that of biological membranes, resulting in enhanced penetration in the stratum corneum, localized depot within the deep skin layers and consequently sustained release of dermally active compounds with a reduction of the amount of drug absorbed into systemic circulation.
Liposome formulations of a-tocopherol acetate confirmed their efficacy, with increased drug deposition in skin as compared with control formulations. Liposome dispersions also significantly increased a-tocopherol photostability, but have no effect on skin deposition.
Darvin, M. Zastrow, L Sterry, W. Lademann, J. Effect of Supplemented and Topically Applied Antioxidant Substances on Human Tissue. Skin Pharmacol Physiol 2006;19:238–247