CYCLODEXTRINS 187 (3) Elimination of: © undesired odors or tastes © hygroscopicity (4) Improvement of handling: © of liquid or oily substances as powders © increase in the stability of emulsions In contrast to starch, cyclodextrins and their derivatives are not a nutrient medium for microorganisms. As a result, the use of preservatives in formulations can be reduced. This is a further advantage of cyclodextrins. Detailed studies on the toxicity, mutagenicity, teratogenicity, and carcinogenicity of cyclodextrins and some of their derivatives have been performed (18). These results indicate that cyclodextrins may be harmful to the human organism only at extremely high concentrations. No indication of acute toxicity was observed during animal ex- periments. Since November 2000, 13-cyclodextrin has been licensed in Germany as an additive in food (19). This had already been done in Japan and in the USA some years earlier. Dermatological studies using cyclodextrins have been reported in the literature also (20). The price of cyclodextrins was mainly responsible for the relatively low number of practical applications in different areas. Fortunately, during the last few years prices have decreased and, therefore, further and new applications of cyclodextrins have become possible. EXAMPLES OF THE USE OF C¾CLODEXTRINS The number of patent applications dealing with cyclodextrins in cosmetic and pharma- ceutical applications is enormous. It is not the aim of this article to cite all of them. According to the above-cited advantages for the use of cyclodextrins, some examples will be given. There will be no special differentiation among the cyclodextrin derivatives used in cosmetic formulations. Due to the extremely large number of commercially available products, this information will be far from being complete. Only as examples will some trade names of cyclodextrin-containing cosmetic products be given. PROTECTION OF THE GUEST MOLECULES Protection against light and oxidation. Tea tree oil shows antimicrobial properties. The pure oil is stable for a month in the absence of light and oxygen. Otherwise the terpenes present in the oil react with light and oxygen in the formation of the skin irritant p-cymene. As a cyclodextrin complex, tea tree oil is stable against light and oxygen and therefore the formation of undesired compounds is prevented. The antimicrobial and antiflammatory properties of tea tree oil are not affected by the complex formation (21). Some commercial products are Epicutin-TT © (Chem. Laboratorium Dr. Kurt Richter GmbH) and Pickelex © (Regena Ney Cosmetic). Hydroquinone is used for skin whitening. In aqueous formulations hydroquinone is stable only in a limited-pH range. Therefore stabilizers are normally used. Due to the prevention of the oxidation of hydroquinone, the cyclodextrin complexes have a greater stability. They also show a greater alepigmentation than the hydroquinone itself (22). Kojic acid is another substance used as a whitening agent in cosmetic creams. Its use is

188 JOURNAL OF COSMETIC SCIENCE limited because kojic acid is labile when exposed to light or heat. Due to decomposition it turns to a yellowish brown. The cyclodextrin complex has an improved stability against coloring in the lapse of time. The cyclodextrin complex of kojic acid also has an enhanced skin-whitening effect (23). Peroxyacetic acid is a liquid that is handled as an aqueous solution. It forms solid complexes with ix- and [3-cyclodextrin. These stable powders are easy to handle and they can be used in cosmetic formulations as skin- lightening substances. These complexes also act as mild oxidants with disinfectant properties (24). Protection against loss by evaporation. Volatile compounds like perfumes (25,26) or com- ponents of them (27) are stabilized against evaporation as cyclodextrin complexes. The complexes may be used in powders or liquid formulations. Even in solid form the perfume complexes are used in perfumes. Applying these suspensions on the skin assures a long-lasting effect by slow release of the perfumes. Long-acting perfumes are marked as Vivace © (Shiseido Co.). SOLUBILIZATION OF THE GUEST MOLECULES A large number of cosmetic components are nearly insoluble in water. Only a few examples, such as vegetables oils, hydrocarbons, higher fatty acids and their esters, vitamins, hormones, antiphlogistics, and preservatives are mentioned. All these chemical substances are able to form inclusion complexes with cyclodextrins. As a result, these complexes are more soluble compared to the pure compounds. This effect can be gen- erally used for the formulation of cosmetics (28). Salicylic acid is used for the cleaning of the skin. Its action is mainly antibacterial and keratolytic. The solubility of the acid or its derivatives in aqueous solution is low. The complex with cyclodextrins is much more soluble. Thus, possibly irritating reactions occurring with the free acid are prevented due to better homogeneity. Complexed with cyclodextrins, its disinfectant, bacteriostatic, and keratolytic properties also increase (29). The cyclodextrin complex of salicylic acid is already commercially available (Lipo Chemicals Inc.). It is used in Bioclin Sebo Care Impure Skin Cream © (Ganassini). In many personal care products triclosan acts as a topical antiseptic and disinfectant. It is nearly insoluble in water, moderately soluble in alkaline solutions, and quite soluble in organic solvents. The cyclodextrin complex (Lipo Chemicals Inc.) is soluble in water, giving a clear solution. Menthol has an effect as a cooling agent in different cosmetic products. Menthol is only slightly soluble in water. To increase the solubility, alcohol is normally added. The cyclodextrin complex is freely soluble in water, giving a clear solution without the presence of alcohols (Lipo Chemicals Inc.). In topical anti-aging formulations, retinol is used. It reduced wrinkles and supports the restoration of UV-damaged tissues. Unfortunately, UV light and oxygen initiate chemi- cal reactions of retinol. Thus, during oxidation some peroxidic toxic intermediates are formed. Also, the solubility of retinol is low in aqueous media. Retinol forms complexes with cyclodextrins that are stable in the presence of light and oxygen. Complexes of retinol acetate and retinol palmitate with [3-cyclodextrin are well known. Also, retinoic acid and some of its derivatives form complexes with cyclodextrins (30). Just recently the formation of complexes with •-cyclodextrin have been reported (31). Retinol-