j. Cosmet. sci., 52, 313-324 (September/October 2001) Investigations on the occlusive properties of solid lipid nanoparticles (SLN) S. A. WISSING, A. LIPPACHER, and R. H. MULLER, Department of Pharmaceutics, Biopharmaceutics and Biotechnology, The Free University of Berlin, Kelchstrasse 31, D-12169 Berlin, Germany. Accepted for publication May 31, 2001. Synopsis Skin hydration can be influenced to a great extent by occlusive compounds. Conventional highly occlusive compounds tend to have an unacceptable appearance. Therefore, the development of innovative occlusive topicals is an essential issue regarding the formulation of cosmetic and pharmaceutical preparations. Solid lipid nanoparticles (SLN TM) represent a novel carrier system for controlled release of topical cosmetic and pharmaceutical compounds. In addition to their controlled release characteristics, it has been found that SLN have an occlusive effect. The extent of the occlusive effect depends on various factors such as particle size, applied sample volume, lipid concentration, and crystallinity of the lipid matrix. These factors have been investigated in detail by an in vitro test, and the obtained data give insight into their importance. INTRODUCTION Solid lipid nanoparticles (SLN TM) have been introduced as a novel carrier system for the controlled release of pharmaceutical and cosmetic active compounds (1). Various routes of application, such as oral, i.v., J.p., and dermal have been investigated (2,3). A recent development is the use of SLN in topical cosmetic and pharmaceutical preparations, e.g., creams and gels (4,5). Advantages of SLN in topical formulations are: ß protection of labile incorporated compounds against chemical degradation ß controlled release of incorporated compounds ß a white pigment effect (covering undesired colors of compounds or their degradation products) ß an occlusive effect, inducing enhanced skin hydration, thus leading to wrinkle smoothing and an enhanced penetration into--or specific localization of compounds in--specific skin layers. There are many reports about incorporation of cosmetic and pharmaceutical compounds into SLN and about SLN-related benefits (2,3,6,7). However, very little has been re- ported about the occlusion effect and the SLN parameters affecting the extent of occlu- sion. Occlusion is an important factor for skin hydration and the subsequent effects of the modified penetration of compounds (8-10), and therefore this paper investigates in detail the occlusive properties of SLN and the factors affecting occlusion. 313

314 JOURNAL OF COSMETIC SCIENCE The stratum corneum contains 10-20% water (11). If the water content falls below this value (i.e., if water evaporation from the skin to the atmosphere is increased), the protective layer of the skin is no longer intact and starts to get chapped. In this case, occlusive topicals have to be applied in order to regenerate the water content of the stratum corneum and thus repair the surface of the skin (11). Due to occlusion, water evaporation from the skin to the atmosphere is decreased and water is thus retained within the skin. The stratum corneum swells, which leads to a drug permeation- enhancing effect (12,13). However, many of the topicals with good occlusive properties (e.g., petrolatum, fats, fatty acids, silicon oil, and polyacrylate foils) have an unacceptable cosmetic or aesthetic appearance. Therefore, different w/o and o/w emulsions have been developed (10,11). They represent a compromise between occlusive performance and appearance on the skin. An advantage of SLN is the easily performed incorporation into various topicals such as gels and creams (14). During production, a part of the water is replaced by concentrated aqueous SLN dispersion. Alternatively, creams can be produced with a lower water content and the SLN dispersion is admixed in the last production step. It has been shown that SLN remain intact after incorporation into an o/w cream, i.e., they do not dissolve within the lipid phase if the lipids are chosen carefully (15). That means one can easily combine the advantages of an existing cream or gel with the additional benefits of SLN. The occlusive character of SLN is due to film formation after application to the skin, leading to decreased water evaporation (4,16). To produce SLN and creams with maxi- mum occlusive effect, one needs to know the factors controlling the extent of occlusion. Therefore, in this study the occlusive effect has been investigated in detail regarding dependency on the volume of the sample applied to the skin, SLN particle size, con- centration of the lipid phase, and crystallinity of the lipid phase. Further, to assess the efficiency of SLN suspensions (and SLN added to creams) in enhancing occlusion, a comparison to a conventional cream was made. MATERIALS AND METHODS MATERIALS Cetyl palmirate (Gattefoss•, France), Dynasan 112, 114, and 116 (Contensio, Germany), TegoCare © 450 (Goldschmidt, Germany), sucrose ester 1670 (Mitsubishi-Kogaku Foods Corp., Japan), and Lipofundin 20% N (Braun Melsungen, Germany) were kindly pro- vided as gifts. Ungt. emulsific. aquos. was obtained from Caelo GmbH (Germany), and Tyloxapol © was obtained from Sigma Chemicals. METHODS Production of SLN. SLN were produced using high-pressure homogenization (hot tech- nique) or ultrasonication. The lipids were melted at approximately 85øC, and then the hot surfactant solution was added and mixed for one minute using a high-speed stirrer (Ultra Turrax T25, Janke & Kunkel, Germany) at 8000 rpm. The obtained pre-emulsion was homogenized using a Lab 40 high-pressure homogenizer (APV Deutschland GmbH, Germany) with temperature control, applying a pressure of 500 bar and three homog- enization cycles if not stated otherwise. Details of the production method are described