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j. Soc. Cosmet. Chem., 46, 191-198 (July/August 1995) Stability of all-trans-retinol in cream T. TSUNODA and K. TAKABAYASHI, Laboratory of Development Research, Shiseido Research Center, 1050 Nippa-cho, Kohoku-ku, Yokohama-shi 223, Japan. Received February 1, 1995. Synopsis Among the retinoids, we chose retinol (vitamin A) and studied the stability behavior of all-trans-retinol in creams. We observed thermal isomerization from all-trans-retinol to 13-cis-retinol, and this isomerization was a function of increasing temperature and oil content in creams. In addition, when the possibility of contact between retinol and water in creams was enhanced, retinol could be easily dehydrated to anhydro- vitamin A. Therefore, a balance of oils and water is considered to be important for the stabilizing of retinol in cream. We found that the reduction of all-trans-retinol in cream was caused by compound factors: thermal isomerization by temperature, dehydration by water, decomposition by oxygen, and peroxide in the surfactants or oils used in creams. INTRODUCTION Among the retinoids, which are supposed to induce thickening of the epidermis and thin the stratum corneum and be effective for the treatment of skin diseases (1), retinol is regarded as desirable because of its lower stimulus compared to retinoic acid. How- ever, retinol is said to be unstable in light and oxygen. Some studies on the stability of oil-soluble retinoids in oil are reported (2-4), but in these studies the phenomenon of decrease of retinoids was observed under mixed conditions affected by light, oxygen, lipid peroxide, temperature, and water. Therefore, in order to clarify the influence of each condition and the stabilization countermeasures for application in skin-care cream, we studied the stability behavior of all-trans-retinol, which has a higher physiological activity than other isomers, by means of reverse-phase high-performance liquid chro- matography (HPLC). The possibilities of ultraviolet effects that can cause photo- isomerization (5) of retinol and oxygen effects that can cause oxidation and decompo- sition of retinol are negated by using pure yellow-colored fluorescent light, brown- colored bottles, and a glove box and argon gas blanket for preparing the samples, preservation, and measurement. MATERIALS AND METHODS STORAGE TEST Ten milliliters of 500 ppm retinol (3100 units/mg FLUKA) in ethanolic solution or 191