ANTICELLULITIC MICROSPHERES: IN VITRO ASSESSMENT OF RELEASE BEHAVIOR Svarc, Federico E . 1 ; Daraio, Marta E. 2 ; Arnejo, Norberto A. 1 ; Carballo, Oscar P. 1 ; Debandi, María V. 2 ; François, Nora J. 2 ; Blanco, Alfredo . 1 1 Fabriquimica S. R. L., Buenos Aires, Argentina. 2 Facultad de Ingeniería, Universidad de Buenos Aires, Argentina. e-mail: svarc@fabriquimica.com.ar Key words: Anticellulitic microspheres, controlled release, skin models, Caffeine Short summary The complex formed by Caffeine (CAF), Triethanolamine Hydroiodide (TEAH), Algae Extract (AE), Hedera Helix Extract (HHE) and Ruscus Aculeatus Root Extract (RARE) has a proofed anticellulitic action in vivo. In this work, the complex was loaded into inorganic porous microspheres of 100 nm mean diameter which were included into a typical cosmetic O/W emulsion. The release and permeation of the anticellulite actives was evaluated using different membranes, to determine how realistic they are, when used as models for human skin. On the other hand, we also could compare the influence of a typical cosmetic formulation on the CAF, TEAH, HHE and RARE release. We found that commercial polycarbonate membranes resulted more realistic in simulating the behavior of full thickness porcine ear skin than a polycarbonate membrane with a deposited layer composed of the main lipids of the stratum corneum. We also found that an O/W emulsion significantly hinders drug diffusion from these microspheres, compared to that obtained from an aqueous suspension. The results for the plant extracts are in accord with those obtained for TEAH and CAF. Introduction Transport of hydrophilic or charged molecules through the skin is especially difficult attributable to the lipid-rich nature of the stratum corneum and its low water content. This layer is composed of about 40% lipids, 40% protein, and only 20% water. Transport of lipophilic drug molecules is facilitated by their dissolution into intercellular lipids around the cells of the stratum corneum. Absorption of hydrophilic molecules into skin can occur through „pores‟ or openings of the hair follicles and sebaceous glands, but the relative surface area of these openings is barely 1% of the total skin surface. This small surface area limits the amount of drug absorption. An understanding of the transport behavior of drugs into the emulsion and through the membrane is important for designing an effective topical product. Cellulite (also known as hydrolipodystrophy gynoid, edematofibrosclerotic panniculitis, liposclerosis, lipedema, adiposis edematosa) is a cosmetically unacceptable aesthetic problem; approximately 85% of women over the age of 20 have some degree of this physiological gender-linked condition [1]. It is manifested by an orange peel skin macro relief. Xanthines, like caffeine, are used in anticellulite cosmetics due to their lipolytic activity on fat. The site of action of caffeine is on the adipocytes located in the hypodermis. The cosmetic formulation has to be designed to ensure that caffeine reaches the active site. The complex formed by Caffeine (CAF), Triethanolamine Hydroiodide (TEAH), Algae Extract (AE), Hedera Helix Extract (HHE) and Ruscus Aculeatus Root Extract (RARE) has a proofed anticellulitic action in vivo. Moreover, it was observed that the complex was more effective when it is adsorbed in porous inorganic microparticles of mean diameter 100 nm than in a hydroglycolic solution and the complex was more effective than its individual components alone [2].