j. Soc. Cosmet. Chem., 47, 97-107 (March/April 1996) Influence of formulation type on the deposition of glycolic acid and glycerol in hairless mouse skin following topical in vivo application M. OHTA, C. RAMACHANDRAN, and N. D. WEINER, Cosmetics Laboratory, Kanebo Ltd., Odawara, Kanagawa, Japan (M. O. ), and College of Pharmacy, University of Michigan, Ann Arbor, MI 48109-1065 (C.R., N.D.W.). Received December 1995. Synopsis The kinetics and extent of uptake of glycolic acid and glycerol in various strata of hairless mouse skin following topical in vivo application of several glycolic acid and glycerol formulations were determined. The formulations tested included an aqueous solution, a 30% propylene glycol (PG) aqueous solution, an oil-in-water (O/W) emulsion, a water-in-oil (W/O) emulsion, and two nonionic liposomal systems. The two nonionic liposomal formulations were prepared from: (i) glyceryl dilaurate, cholesterol, and polyoxyethyl- ene-10-stearyl ether (Non-1) and (ii) glyceryl distearate, cholesterol, and polyoxyethylene-10-stearyl ether (Non-2). Each of the test formulations was applied to the skin surface, and after one hour the formulations were removed by swabbing. Deposition profiles in the various strata were then monitored at 0, 1, 2, 4, and 8 h after removal of the formulation. The amounts of glycolic acid in the living skin strata at the end of the 1-h application period (0 hour time point) were in the order: Non-1 = Non-2 = aqueous solution = O/W emulsion = W/O emulsion 30% PG solution. The amounts of glycolic acid at the 8-h time point were in the order: Non-1 = Non-2 = O/W emulsion = W/O emulsion aqueous solution = 30% PG solution. The amounts of glycerol in the living skin strata at the end of the l-h application period were in the order: Non-2 = Non-! O/W emulsion = aqueous solution = 30% PG solution W/O emulsion. At 8 h, the amounts of glycerol in the living skin strata were in the order: Non-2 Non- 1 O/W emulsion = aqueous solution = W/O emulsion 30% PG solution. Although both glycolic acid and glycerol are hydrophilic, systemic absorption of glycolic acid was higher than that of glycerol. The Non-2 liposomal formulation appears to be the most efficient of all the formulations tested, since it delivered higher amounts of glycolic acid and glycerol into the stratum corneum and the living skin strata while retarding systemic absorption. INTRODUCTION Glycolic acid and glycerol are small water-soluble molecules that are widely used in cosmetic formulations to improve moisturization and appearance of skin. Glycerol is one of the most commonly used humectants in cosmetics (1). Glycolic acid is reported to smooth the skin's surface and create a more uniform skin tone (2,3). Although the mechanisms of therapeutic action of glycolic acid still remain unknown, it has been 97

98 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS employed in cosmetic and skin care products for several years with great success. However, few reports on the deposition of glycolic acid and glycerol into skin after topical application have been published. Some in vitro transport studies were carried out to determine the permeation of glycolic acid (4) and glycerol (5) through the skin, but their accumulation in various strata of the skin following topical application was not determined. In the cosmetic industry, it is of interest to determine the extent to which the ingredients of the formulation accumulate in the stratum corneum and to determine whether or not they are transported into the living epidermis and beyond. The stratum corneum is the most important barrier to penetration through the skin and also acts as a reservoir for molecules applied to the skin (6). For some cosmetic ingre- dients such as glycerol, it is more important that they be retained in the stratum corneum in order to maintain skin moisturizing effects than to penetrate into the living strata. On the other hand, it may be necessary to transport compounds such as glycolic acid into the living skin strata in order for them to exert their therapeutic action resulting in improvement of the appearance of the skin. Thus, for optimum clinical effects it is necessary to design a formulation that will optimize delivery of actives to the appropriate skin strata. The purpose of this study is to investigate the kinetics of deposition of glycolic acid and glycerol in various strata of hairless mouse skin following topical in vivo application of a variety of formulations. MATERIALS AND METHODS MATERIALS Glycolic acid and propylene glycol (PG) were obtained from Sigma (St. Louis, MO). Glycerol was obtained from J. T. Baker Chemical Co. (Phillipsburg, NJ). The synthetic nonionic lipids, glyceryl dilaurate (GDL), glyceryl distearate (GDS), and polyoxyeth- ylene- 10-stearyl ether (POE- 10), as well as cholesterol (CH), were provided by IGI, Inc. (Little Falls, NJ). Tween 60, Arlacel 83, and Span 60 were purchased from CIC (Wilmington, DE). Paraffin soft was obtained from Sargent-Welch (Skokie, IL), and the mineral oil used was from Mallinckrodt (Paris, KY). The water used was double- distilled and deionized with a Millipore Milli-Q © system. 14C-Glycolic acid was ob- tained from Chemsyn Science Laboratories (Lenexa, KA). 3H-Glycerol was obtained from NEN (Boston, MA). METHODS Preparation of formulations Nonionic liposomal formulations. Two nonionic liposomal formulations, one containing glyceryl dilaurate / cholesterol / polyoxyethylene- 10-stearyl ether (Non- 1), and the other glyceryl distearate/cholesterol / polyoxyethylene-10-stearyl ether (Non-2), at a weight percent ratio of 57/15/28, were prepared by the syringe method. Appropriate amounts of the lipids were accurately weighed in a scintillation vial. The vial was then capped and heated with stirring at 75øC in a water bath to melt the lipids. The lipid melt was then drawn into a syringe preheated at 75øC and maintained at 75øC in a water bath. A second syringe containing appropriate amounts of 40 mg/ml glycolic acid or 25 mg/ml