J. Cosmet. Sci., 55, 233-252 (May/June 2004) Vitamin A palmitate photostability and stability over time M. E. CARLOTTI, V. ROSSATTO, M. GALLARATE, M. TROTT A, and F. DEBERNARDI, Dipartimento di Scienza e Tecnologia def Farmaco (M.E.C., M.G., M.T., F.D.), and Dipartimento di Chimica Analitica (V.R.), Universita degli Studi di Torino, 10125 Turin, Italy. Accepted for publication January 26, 2004. Synopsis Vitamin A palmitate photostability in relation to UVA and UVB was tested in hydroxy ethyl cellulose hydrogels at pH 4.0, 5 .6, 7 .0, and 8.0, alone and with the addition of sunscreens (3,4-methylbenzi­ lidencamphor or butyl methoxy dibenzoylmethane) or an antioxidant (butylated hydroxy toluene). The photostability of vitamin A palmitate was also tested in encapsulated systems (Tagravit® A 1 microcapsules, Lipotec® liposomes, phosphatidylcholine liposomes, and Lipotec® nanocapsules) dispersed in gels at pH 5.6 and 7 .0. The stability of retinyl palmitate over time in hydroxy ethyl cellulose hydrogels at pH 5 .6 and 7 .0 (stored one month at 25°C or 40°C), alone or with butylated hydroxy toluene, was also tested. The stability of retinyl palmitate over time in encapsulated systems, dispersed in gels at pH 5 .6 and 7 .0, was also studied. 0/W emulsions were also prepared to compare the stability of vitamin A palmitate introduced in a lipophilic/hydrophilic medium (0/W emulsions) and a hydrophilic medium (hydrogels). HPLC analysis showed that encapsulated systems such as Lipotec® nanocapsules, Tagravit® A 1 microcapsules, phosphati­ dylcholine liposomes, and Lipotec® liposomes protect the vitamin A ester over time from hydrolysis and from oxidation to retinaldeide and retinoic acid, and that Lipotec® nanocapsules and phosphatidylcholine liposomes also improve the vitamin's photostability. A change in pH (from 5.6 to 7.0) of the gels did not influence the vitamin ester's stability. pH levels of 4.0 and 8.0 determined a decrease in the stability of retinyl palmitate in the gels. A high concentration of sunscreens improved the photostability of retinyl palmitate in the gels at pH 5 .6 and 7 .0. Butylated hydroxy toluene protected retinyl palmitate from degradation induced by light at all the pH levels studied and by heat at pH 5 .6 and 7 .0, as can be seen from the study of the photostability of vitamin A palmitate under UVB and UVA and of stability over time. Rheological studies showed a slight decrease in the viscosity of the gels after UVB-UVA irradiation and a higher decrease in the viscosity of the gels and the emulsions after storage at 25°C and 40°C. This decrease can be attributed to a partial degradation of hydroxy ethyl cellulose and of emulsifier, as can be seen from the decrease in shear stress versus shear rate values under these conditions of storage, denoting a depoly­ merization of the rheological modifier. INTRODUCTION Vitamin A and its esters are widely used as active components in cosmetic and derma- Address all correspondence to M. E. Carlotti. 233

234 JOURNAL OF COSMETIC SCIENCE tological preparations. They take part in the regulation of epidermal cell growth, inhibit the final step of keratinization, participate in the collagen synthesis process, prevent atrophy of connective tissue, enhance glycosaminoglycane synthesis, and are essential in the reproduction of basal membrane cells (1). A characteristic feature of retinoids is their sensitivity to ultraviolet radiation. Both UVB and UV A radiation reduce the vitamin A content of the human epidermis (2). UV irradiation can deplete epidermal vitamin A, and thus the hypothesis that UV-induced depletion of vitamin A in sun-exposed skin is involved in the pathogenesis of skin cancers and skin aging has been suggested (3 ). The chemical nature of retinoids, con­ sisting of polyunsaturated polar lipids, makes them able to interact with oxygen and UV or visible light to produce reactive oxygen species and free radicals. Sun-exposed epi­ dermis contains less retinyl ester than adjacent unexposed skin. UV light decreases the content of vitamin A in the epidermis as a function of time and UV dose (4). The vehicle used influences the in vivo skin absorption of vitamin A. Percutaneous absorption is modulated by the skin's pH and integrity, hydration conditions, the mode of application, the oil/water partition coefficient, the ionization state, and vitamin A palmitate concentration (5). If the vehicle hinders absorption, vitamin A remains on the skin surface where it is more exposed to UV radiation. The principal reason for vitamin A degradation is the oxidation process. Liposome systems protect vitamin A from oxidation and increase vitamin A stability during UV irradiation, when the liposomes are dispersed in a polyacrylate gel as a vehicle (1). This fact is due not only to the antioxidant nature of phospholipids, but also to the specifically organized phospholipid by-layers, within which the vitamin A is encapsulated. Liposomes are possible vehicles to protect drugs against UV radiation (6) when they are incorporated in a polyacrylate gel as delivery vehicles. Solid lipid nano­ particles (SLN) also possess a number of advantageous features for the topical route in particular, they influence the protection and release of incorporated substances (6,7). In our previous paper (8) vitamin A and vitamin A palmitate stability in ethanol and in an O/W emulsion over time and under UVB and UV A radiation was studied. The present study aims to evaluate the best vehicle for retinyl palmitate to protect it from degradation over time and from UV radiation. The photostability and the kinetic stability of the vitamin A ester in hydroxy ethyl cellulose gel at two different pHs and in O/W emulsion were tested by incorporating the vitamins in different vehicles such as liposomes, poly-methylmethacrylate microcapsules, and double-coated nanocapsules, to evaluate the influence of vehicle, formulation, and pH on their stability. The photo­ degradation of hydroxy ethyl cellulose gels and of the components of the O/W emulsion was also investigated, by monitoring the viscosity under irradiation conditions. The protection of the formulations by the addition of sunscreens (3,4-methylbenzilidene camphor and butyl methoxy dibenzoyl methane) and an antiradical scavenger (butylated hydroxy toluene) to the formulations was also studied and compared with the protection provided by the vehicles alone. Penetration of vitamin A palmitate through the skin was also studied, as the amount of vitamin remaining on the skin surface can be photode­ graded.