title: Semisolid SLN dispersions for topical application: influence of formulation and production parameters on viscoelastic properties.
abstract: Aqueous solid lipid nanoparticle (SLN) dispersions with a high lipid content up to 35% and viscous to semisolid consistency were produced by a high pressure homogenization process. Despite their high lipid content and viscosity these dispersions preserved their colloidal size range. The SLN dispersions were compared to nanoemulsions and microparticle dispersions with regard to particle size, viscoelastic properties and formation of a semisolid gel structure. Viscoelastic measurements including oscillation stress sweep tests and oscillation frequency sweep tests demonstrated that the existence of a solid particle matrix with a particle size in the nanometer range is a prerequisite to form a semisolid dispersion having the appropriate consistency for topical application. Striking differences were observed between solid lipid micro- and nanodispersions of the same composition. Particle size reduction resulted in an 80-fold increase of the elastic modulus. Particle size distribution, the physical state of the dispersed lipid phase and the emulsifier concentration have been identified as further key factors for the viscoelastic properties and gel structure of the lipid nanodispersions. By conducting oscillation measurements it was possible to relate the stability of lipid dispersions to specific rheological parameters therefore providing a sensitive tool in stability assessment. Changing the production process from a 40 ml batch to a 2 l batch turned out to have an influence on the colloidal structures of semisolid SLN dispersions. Consistency increased but particle size and ratio of elastic to viscous properties stayed in the same range.
authors.affiliation: Department of Pharmaceutics, Biopharmaceutics and Biotechnology, Free University of Berlin, D-12169 Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Lippacher
authors.forename: R H
authors.initials: RH
authors.lastname: Müller
authors.forename: K
authors.initials: K
authors.lastname: Mäder
mesh_terms: D000287:Administration, Topical; D002626:Chemistry, Pharmaceutical; D004355:Drug Stability; D004356:Drug Storage; D004548:Elasticity; D004655:Emulsions / Q000008:administration & dosage* / Q000138:chemical synthesis*; D004952:Esters; D005782:Gels; D007850:Lauric Acids / Q000008:administration & dosage / Q000737:chemistry; D008055:Lipids / Q000008:administration & dosage* / Q000138:chemical synthesis*; D036103:Nanotechnology / Q000379:methods*; D010168:Palmitates / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D012212:Rheology; D013229:Stearic Acids / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity
chemical_list: D004655:Emulsions; D004952:Esters; D005782:Gels; D007850:Lauric Acids; D008055:Lipids; D010168:Palmitates; D013229:Stearic Acids; C030358:lauric acid; C031183:stearic acid; D013395:Sucrose; C006957:cetyl palmitate