J. Cosmet. Sci., 57, 487-494 (November/December 2006) Development of a w/o/w emulsion for chemical peeling applications containing glycolic acid GULGUN YENER and AIDA BAITOKOVA, Istanbul University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Cosmetics Section, Beyazit 34116, Istanbul, Turkey. Accepted for publication August 3, 2006. Presented as a poster, "Development of a new topical formulation for chemical peeling," at the Skin and Formulation Symposium, Paris, October 23-24, 2003. Synopsis Glycolic acid is a member of the AHA family, which occurs naturally in foods and has been used for centuries as a cutaneous rejuvenation treatment. It is used in many cosmetic products as an exfoliant and moisturizer. When glycolic acid is used in greater amounts, however, there are greater cosmetic benefits but also potential for skin irritation as far as burning increases. The aim of this work was to investigate the feasibility of a topical delivery system as a multiple emulsion combining glycolic acid, strontium nitrate, and dexpanthenol in order to optimize the acid's cosmetic properties and lowering its side effects. INTRODUCTION Glycolic acid (GA), a member of the hydroxy acid (AHA) family, is one of the most commonly used superficial chemical peeling agents, used to improve a variety of skin disorders. Recently it has proved to be a versatile peeling agent, and it is now widely used to treat many defects of the epidermis and papillary dermis in a variety of strengths ranging from 20% to 70%, depending on the condition being treated (1). Maintenance use of GA in low concentrations is effective for the control of various keratinization disorders, such as xerosis, ichtyosis, acne, and "age spot" keratoses. When used in high concentrations it causes epidermolysis, resulting in the regeneration of new epidermal and dermal tissue, and is beneficial for the treatment of actinic and seborrheic keratoses, warts, wrinkles, acne scars, and pigmentary changes such as postinflammatory hyper­ pigmentation and melasma (2,3). GA solutions with a concentration of more than 20% can only be used by dermatologists in practice, but GA is also available at lower concentrations as home-care products (4). Many reports have indicated that local appli­ cation of GA may induce varying degrees of sensory irritation (stinging, burning, and itching) reactions, especially at higher concentrations (5,6). The main problem related to GA in cosmetic applications is its irritative properties, and this generates the rationale for studies of cosmetic formulations with reduced adverse reactions. For this purpose, different types of microparticulate systems have been evalu­ ated: liposomes, liposomes modified by chitosan, and chitosan microspheres (7). Inves- 487

488 JOURNAL OF COSMETIC SCIENCE tigations regarding the feasibility of topical controlled delivery systems, loading GA in order to optimize its cosmetic properties and lowering its side effects, have been going on. Procedural side effects and the complications of chemical peeling are known to be best controlled by careful preoperative screening (8) and by preparing the most suitable formulation. Strontium salts have been demonstrated to inhibit sensory irritation and inflammation when applied topically (9-11), and it was reported that dexpanthenol was found to create accelerated and improved wound healing (12). Water-in-oil-in-water (w/o/w) multiple emulsions are composed of oily globules dis­ persed in an aqueous phase and which themselves contain aqueous microglobules. These multiple systems have been widely used over the last twenty years in pharmaceuticals ( 13, 14) and cosmetics (15, 16). The main applications of these systems are in the en­ trapment of fragile drugs such as ascorbic acid (17) and proteins (18) or drugs with undesirable side effects, and as a formulation for controlled release preparations (19). Multiple emulsions were reported to release their contents more slowly than w/o and o/w emulsions (20). Taking all these findings into account, the aim of this study was to investigate the properties of this chemical peeling substance (GA) together with a wound-healing agent (dexpanthenol-D) and a chemically induced sensory irritation-suppressing agent (stron­ tium nitrate-S) in a novel cosmetic delivery system, in multiple emulsions for the first time. MATERIALS AND METHODS MATERIALS This study employed glycolic acid (Merck), dexpanthenol (Fluka), strontium nitrate (Riedel de Haen), Abil EM 90 (cetyl dimethicone copolyol) (Goldschmidt), and Tween 80 (Merck). It also employed a SOIF H-ZSX/Syne Master 5 l0S microscope, a Brookfield DVII viscometer, and a KIKA Labortechnik RW20 DZM mechanical mixer. METHODS Production of multiple emulsions. Multiple emulsions are complex, inherently unstable systems that are unlikely to be commercially acceptable as drug delivery systems until the problems of their instability in vitro and in vivo are solved (21). It has been reported that to improve photostability, attempts were made to polymerize appropriate mono­ mers in the aqueous phases of w/o/w multiple emulsions. The aim was to reduce the potential for coalescence of the internal aqueous droplets. Because the preparation of a w/o/w system is a two-step procedure, it is possible to modify the primary aqueous phase, which subsequently becomes the continuous aqueous phase. Each aqueous phase can be gelled by in situ polymerization. The aim of our research was to prepare stable w/o/w multiple emulsions and to ensure that their physiochemical properties were not modified by adding the chosen cosmetic actives (glycolic acid, strontium nitrate, and dexpanthenol). We obtained multiple