title: Control over Particle Size Distribution by Autoclaving Poloxamer-Stabilized Trimyristin Nanodispersions.
abstract: Lipid nanoparticles are under investigation as delivery systems for poorly water-soluble drugs. The particle size in these dispersions strongly influences important pharmaceutical properties like biodistribution and drug loading capacity; it should be below 500 nm for direct injection into the bloodstream. Consequently, small particles with a narrow particle size distribution are desired. Hitherto, there are, however, only limited possibilities for the preparation of monodisperse, pharmaceutically relevant dispersions. In this work, the effect of autoclaving at 121 °C on the particle size distribution of lipid nanoemulsions and -suspensions consisting of the pharmaceutically relevant components trimyristin and poloxamer 188 was studied. Additionally, the amount of emulsifier needed to stabilize both untreated and autoclaved particles was assessed. In our study, four dispersions of mean particle sizes from 45 to 150 nm were prepared by high-pressure melt homogenization. The particle size distribution before and after autoclaving was characterized using static and dynamic light scattering, differential scanning calorimetry, and transmission electron microscopy. Asymmetrical flow field-flow fractionation was used for particle size distribution analyses and for the determination of free poloxamer 188. Upon autoclaving, the mean particle size increased to up to 200 nm, but not proportionally to the initial size. At the same time, the particle size distribution width decreased remarkably. Heat treatment thus seems to be a promising approach to achieve the desired narrow particle size distribution of such dispersions. Related to the lipid content, suspension particles needed more emulsifier for stabilization than emulsion droplets, and smaller particles more than larger ones.
authors.affiliation: Technische Universität Braunschweig, Institut für Pharmazeutische Technologie , Mendelssohnstraße 1, 38106 Braunschweig, Germany.|Zentrum für Pharmaverfahrenstechnik, Franz-Liststraße 35a, 38106 Braunschweig, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Göke
authors.affiliation: Technische Universität Braunschweig, Institut für Pharmazeutische Technologie , Mendelssohnstraße 1, 38106 Braunschweig, Germany.
authors.forename: Elin
authors.initials: E
authors.lastname: Roese
authors.affiliation: Technische Universität Braunschweig, Institut für Pharmazeutische Technologie , Mendelssohnstraße 1, 38106 Braunschweig, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Arnold
authors.affiliation: Department of Physics, Chemistry and Pharmacy, University of Southern Denmark , Campusvej 55, 5230 Odense M, Denmark.
authors.forename: Judith
authors.initials: J
authors.lastname: Kuntsche
authors.affiliation: Technische Universität Braunschweig, Institut für Pharmazeutische Technologie , Mendelssohnstraße 1, 38106 Braunschweig, Germany.|Zentrum für Pharmaverfahrenstechnik, Franz-Liststraße 35a, 38106 Braunschweig, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Bunjes
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D000067493:Dynamic Light Scattering; D045703:Emulsifying Agents / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D014280:Triglycerides / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D045703:Emulsifying Agents; D014280:Triglycerides; D020442:Poloxamer; C036694:trimyristin
keywords: asymmetrical flow field-flow fractionation (A4F); autoclaving; differential scanning calorimetry; laser diffraction; lipid nanoparticles; particle size distribution; photon correlation spectroscopy