322 JOURNAL OF COSMETIC SCIENCE OCCLUSION--COMPARISON TO A CONVENTIONAL CREAM In order to assess the occlusion properties of SLN dispersions, an occlusion test was performed in which they were compared to an occlusive standard cream system. The o/w-cream ungt.emulsif. aquos. DAB 1998 (21), which is an o/w cream with 30% lipid phase and 70% water phase, was used for comparison. An o/w cream was taken as test system, because SLN dispersions have water as continuous phase. The SLN dispersion in this study (CPZ) consisted of 30% lipid (cetyl palmitate) for better comparison. Sucrose stearic acid ester served as emulsifier. Sucrose esters are nonionic sugar-derived surfac- rants presenting many advantages. They are non-toxic, biodegradable, and approved as food additives due to their high safety rating (22). Furthermore, sucrose esters have an antiirritant effect, show antibacterial action, and give a smooth consistency to emulsions (23). Although not widely used in Europe and the United States, they have found an extensive market in cosmetics and food applications in Japan (24). Applying this aque- ous SLN dispersion of identical lipid content yielded a high occlusion effect with an occlusion factor of 50 after six hours, as can be seen in Figure 6. Particularly at the first time point after six hours, the higher occlusion effect of the SLN dispersion compared to the standard cream system is pronounced. In comparison, the value of the occlusion factor F of water-containing hydrophilic ointment is 41. But even after 24 hours and 48 hours, the higher occlusion factor of the SLN dispersion is clearly visible. The higher occlusion effect of the SLN dispersion can be attributed to the solid state of the dispersed nanoparticles. CONCLUSIONS The current investigations have shown that the choice of particle size, lipid concentra- tion, applied sample volume (lipid mass), and crystallinity of the matrix material plays 70- 60 50 40 30 20 10 6h 24h 48h ß cPz [] o/w cream Figure 6. Comparison of occlusion factors caused by SLN formulation (CPZ) and conventional o/w cream.
OCCLUSIVE PROPERTIES OF SLN 323 an important role for the occlusion of a system. Depending upon the needs of a carrier system, SLN dispersions and formulations with high or low occlusive characteristics can be produced and designed in a controlled way. Our studies show that the conditions for optimized occlusivity are a particle size of about 200 nm, a minimum lipid mass of 3.7 mg/cm 2, and a high degree of crystallinity of the lipid matrix. REFERENCES (9) (10) (11) (1) R. H. Mfiller and J. S. Lucks, Arzneistoffrilger aus resten Lipidteilchen, Feste Lipidnanosphilren (SLN), European Patent No. 0605497 (1996). (2) R. H. Mfiller, W. Mehnert, J. S. Lucks, C. Schwarz, A. zur Mfihlen, H. Weyhers, C. Freitas, and D. Rfihl, Solid lipid nanoparticles (SLN)--An alternative colloidal carrier system for controlled drug delivery, Eur. J. Pharm. Biopharm., 41, 62-69 (1995). (3) R. H. Mfiller, K. Milder, and S. Gohla, Solid lipid nanoparticles (SLN) for controlled drug delivery--A review of the state of the art, Eur. J. Pharm. Bzopharm., 50, 161-177 (2000). (4) R.H. Mfiller and A. Dingier, The next generation after the liposomes: Solid lipid nanoparticles (SLN TM, Lipopearls•M) as dermal carrier in cosmetics, Eurocosmetics, 7/8, 19-26 (1998). (5) V. Jenning, Feste Lipid-Nanopartikel (SLN) al• Tr•ersystem fiir die dermale App/ikation yon Retinol: Wirkstoffinkorporation, -freisetzung und Strukmr, Ph.D. Thesis, FU Berlin (1999). (6) A. Dingler, G. Hildebrand, H. Niehus, and R. H. Mfiller, Cosmetic anti-aging formulation based on vitamin E-loaded solid lipid nanoparticles, Proe. Int. Symp. Control. Release Bioact. Mater., 25,433-434 (1998). (7) V. Jenning, S. Gohla, and R. H. Mfiller, Solid lipid nanoparticles (SLN): Effect of homogenization parameters on drug stability, Proc. 2 " World Meeting APGI/APV, 619-620 (1998). (8) V. Jenning, A. Gysler, M. Schilfer-Korting, and S. Gohla, Vitamin A loaded solid lipid nanoparticles for topical use: Occlusive properties and drug penetration into porcine skin, Eur. J. Pharm. Biopharm., 49, 211-218 (2000). V. Jenning, M. Schilfer-Korting, and S. Gohla, Vitamin A loaded solid lipid nanoparticles for topical application: Drug release properties. J. Control. Release, 66, 115-126 (2000). B. W. Barry, "Skin Transport," in Dermatologieal Formulations, B. W. Barry, Ed. (Marcel Dekker, New York, 1983), pp. 95-117. J. Ziegenmeyer, "Biopharmazeutische Aspekte bei der Anwendung von Dermatika," in Dermatika, R. Niedner and J. Ziegenmeyer, Eds. (Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, 1992), pp. 243-3O8. (12) D. E. Wurster and S. F. Kramer, Investigations of some factors influencing percutaneous absorption, J. Pharm. Sci., 50, 288-293 (1961). (13) B.W. Barry, D. Southwell, and R. Woodford, Optimization of bioavailability of topical steroids: Penetration enhancers under occlusion, J. Inve•t. Dermatol., 82, 49-52 (1984). (14) R.H. Mfiller and A. Dingier, Feste Lipid-Nanopartikel (Lipopearls TM) als neuartiger Carrier ffir kosmetische und dermatologische Wirkstoffe, Pharmazeutische Zeitung/Dermopharmazie, 49, 11-15 (1998). (15) A. Dingier, Feste Lipid-Nanopartikel als kolloidale Wirkstoffir•ersysteme zur dermalen Applikation, Ph.D. Thesis, FU Berlin (1998). (16) S. A. Wissing, K. Milder, and R. H. Mfiller, Solid lipid nanoparticles (SLN)--A novel carrier for UV blockers, Eur. J. Pharm. Biopharm. (submitted). (17) R. H. Mfiller, A. Dingier, T. Schneppe, and S. Gohla, "Large Scale Production of Solid Lipid Nano- particles (SLN) and Nanosuspensions (DissoCubes)," in D. Wise, Ed., Handbook of Pharmaceutical Release Technology (Marcel Dekker, New York, 2000), pp. 359-376. (18) T. de Vringer, Topical preparation containing a suspension of solid lipid particles, European Patent No. 91200664 (1992). (19) S. A. Wissing and R. H. Mfiller, A novel sunscreen system based on tocopherol acetate incorporated into solid lipid nanoparticles (SLN), Int. J. Cosm. Sci. (in press).
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