title: Physicochemical investigations on the structure of drug-free and drug-loaded solid lipid nanoparticles (SLN) by means of DSC and 1H NMR.
abstract: A solid lipid nanoparticle (SLN) formulation, based on the lipid Imwitor 900, was developed for the incorporation of the poorly water soluble drug RMEZ98. Physicochemical investigations were undertaken to examine the structure and physical stability of the selected lipid as colloidal dispersion in comparison to the bulk material. Using differential scanning calorimetry (DSC) and proton nuclear magnetic resonance (1H NMR) it could be assessed the influence of the incorporated drug on the structure of the lipid matrix. Investigation of mixtures of Imwitor 900 and RMEZ98 showed an increasing effect on the melting/recrystallization behaviour with increasing drug content (5-30%). DSC and 1H NMR results revealed the formation of a crystalline matrix of SLN when prepared by high pressure homogenization excluding, therefore, the phenomenon of supercooled melt. After preparation of RMEZ98-loaded SLN, the drug remained inside the lipid matrix; however, it exhibited only a small effect on the recrystallization behaviour of Imwitor 900 at the lowest payload required for a therapeutic effect (4% m/m with regard to the lipid matrix). Furthermore, the incorporation of RMEZ98 revealed no distinct influence on the particle size distribution. Imwitor 900 proved to be a suitable lipid for the drug RMEZ98, i.e. possessing a sufficient loading capacity and simultaneously physical stability.
authors.affiliation: Department of Pharmaceutics, Biopharmaceutics and Biotechnology, Free University of Berlin, PharmaSol GmbH2, Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Zimmermann
authors.forename: E B
authors.initials: EB
authors.lastname: Souto
authors.forename: R H
authors.initials: RH
authors.lastname: Müller
mesh_terms: D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D004578:Electron Spin Resonance Spectroscopy; D007834:Lasers; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008863:Microspheres; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000032:analysis*; D017785:Photons; D012542:Scattering, Radiation; D013696:Temperature
chemical_list: D008055:Lipids; D008081:Liposomes; D004364:Pharmaceutical Preparations