FUNCTIONAL PROPERTIES OF GLYCERIN 233 reported are consistent with the hypothesis that the beneficial effects of glycerol on skin condition are due to its physical effects on the status of water in the outer layers of the stratum corneum. This may be the result of glycerol interactions with the stratum corneum lipid structures or proteins, altering their water-binding and/or hydrophilic properties." This hypothesis correctly anticipates research findings revealing the influ- ence of glycerol on the lipid bilayer to be published within the next few years. A paper published by Froebe (8) in 1990 reports the prevention of stratum corneum phase transitions in vitro by glycerol and describes this phenomenon as an alternate mechanism for skin moisturization. Since intercellular lipids have an integral role in the barrier function of the stratum corneum, it had been proposed by Friberg and Osborne (9) that maintaining the lipids in a liquid state is required for optimal barrier function in preventing water loss. This research demonstrated that the addition of glycerol to a mixture of stratum corneum lipids in vitro inhibits the transition from liquid to solid crystals even when the water content is reduced by low ambient humidity (6% RH). Glycerol does not act as a humectant at 6% RH, either when tested alone or when incorporated into the model lipids. Therefore, the researchers concluded that in a dry atmosphere glycerol acts as a skin moisturizer by inhibiting the lipid phase transition from liquid to solid crystal, rather than by acting as a humectant. They claimed that this represents an alternate, more likely molecular mechanism of action for glycerol. Further support for the above study and its conclusions are provided in an article by Friberg (10) entitled "Micelies, microemulsions, liquid crystals, and the structure of stratum corneum lipids." A phase diagram is included that shows the liquid crystal layered structure to be changed to a crystal structure when the water content is reduced below a certain level. This change is theorized to have a drastic effect, in vivo, on the appearance and smoothness of the skin. An article by Rawlings (11) provides further support for glycerol's multidimensional activities. Ft-om these studies, it is proposed that the properties of glycerol as a humec- tant, occlusive, and as a lipid phase-modulating molecule, are likely to contribute to the improvements in stratum corneum desquamatory enzyme activities and desquamation itself. The researchers believe that one of the major beneficial actions of glycerol- containing moisturizers in vivo is to aid in the enzymatic digestion of superficial des- mosomes in subjects with skin xerosis, thus improving the desquamatory process. In a paper presented by Shapiro (12) at the First International Symposium on Cosmetic Efficacy, results of a five-day double-blind clinical study to determine the ultrastructural changes in skin following use of high-glycerin (25% and 40%) therapeutic moisturizers are presented. Test materials were applied to the volar forearms twice a day. Electron microscopic examination of stained punch biopsies of the test sites and untreated control site revealed that both high-glycerin products penetrated the entire thickness of the stratum corneum and provided expanded appearance, with no identifiable structural changes evident in deeper epidermal or derreal layers. Pure glycerin appeared to pen- etrate minimally and have little or no effect on the appearance of the stratum corneum. The researchers stated that "bulking" of the stratum corneum with a glycerin reservoir, without disruption of the liquid crystal/lamellar structure, is believed to enhance the resilience of skin exposed to harsh climatic conditions and helps explain the sustained skin healing observed following use of these products. These studies also suggest a role

234 JOURNAL OF COSMETIC SCIENCE for a well-formulated glycerol composition in normalization of barrier function that is essential in healing of dry skin and possibly wound healing. RECENT STUDIES Substantiation for glycerol's role in normalizing barrier function is supported by recent research (13) conducted by Fluhr et al. Two studies were performed to evaluate the influence of glycerol on the recovery of damaged corneum barrier function. Measure- ments of transepidermal water loss (TEWL) and capacitance were conducted in a three- day followup after tape stripping (study 1) and in a seven-day followup after barrier damage due to repeated washing with sodium lauryl sulfate (study 2). In study 1, a faster barrier repair as measured by reduced TEWL was shown at the glycerol-treated sites. Significant differences between glycerol open vs untreated and glycerol occluded vs untreated were observed at day 3. In study 2, a faster barrier repair was seen in glycerol-treated sites, with significant differences between untreated and base-treated sites seven days after the end of treat- ment. Stratum corneum hydration showed highest values in glycerol-treated sites after three days of treatment. Glycerol is claimed to create a stimulus for barrier repair and to improve stratum corneum hydration. Since the glycerol-induced recovery of barrier function and stratum corneum hydration were observed even seven days after the end of treatment, the researchers regard glycerol as a barrier stabilizing and moisturizing agent. A paper published in 1998 (14) by researchers at Shiseido and at the UCSF Department of Dermatology entitled "Low humidity stimulates epidermal DNA synthesis and am- plifies the hyperproliferative response to barrier disruption: Implications for seasonal exacerbations of inflammatory dermatoses" provides important therapeutic insights. The results confirm the experiences of many individuals with skin conditions such as atopic dermatosis and psoriasis that these conditions tend to worsen during the winter season, when humidity is much lower. Their studies on murine skin demonstrated that seasonal changes caused by low relative humidity can be prevented either by occlusion with materials such as petrolatum, or application of a 10% glycerin solution in water. Results show that increasing stratum corneum moisture content, whether by occlusion or by humectant treatment, prevents or reverses the development of epidermal hyperplasia. INFLUENCE OF FORMULATION VARIABLES ON THE EFFICACY OF GLYCEROL Future research certainly will provide additional understanding of glycerol's numerous benefits as a functional skin care active. I will now summarize available information related to formulation of glycerol in skin care products with the aim of optimizing performance and of enhancing cosmetic aesthetics. Several publications offer insights on the influence of formulation variables on the efficacy of glycerol (12,13,15,17) however, much information in this domain falls within the category of industrial expertise and know-how. A cosmetic chemist is faced with a significant formulation challenge when formulating with glycerol at levels beyond 10% because of its high viscosity and the tackiness that