title: Nanoparticulate Impurities in Pharmaceutical-Grade Sugars and their Interference with Light Scattering-Based Analysis of Protein Formulations.
abstract: OBJECTIVE
  In the present study we investigated the root-cause of an interference signal (100-200 nm) of sugar-containing solutions in dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) and its consequences for the analysis of particles in biopharmaceutical drug products.
  
  
  METHODS
  Different sugars as well as sucrose of various purity grades, suppliers and lots were analyzed by DLS and NTA before and (only for sucrose) after treatment by ultrafiltration and diafiltration. Furthermore, Fourier transform infrared (FTIR) microscopy, scanning electron microscopy coupled energy-dispersive X-ray spectroscopy (SEM-EDX), and fluorescence spectroscopy were employed.
  
  
  RESULTS
  The intensity of the interference signal differed between sugar types, sucrose of various purity grades, suppliers, and batches of the same supplier. The interference signal could be successfully eliminated from a sucrose solution by ultrafiltration (0.02 μm pore size). Nanoparticles, apparently composed of dextrans, ash components and aromatic colorants that were not completely removed during the sugar refinement process, were found responsible for the interference and were successfully purified from sucrose solutions.
  
  
  CONCLUSIONS
  The interference signal of sugar-containing solutions in DLS and NTA is due to the presence of nanoparticulate impurities. The nanoparticles present in sucrose were identified as agglomerates of various impurities originating from raw materials.
authors: Coriolis Pharma, Am Klopferspitz 19, 82152, Martinsried-Munich, Germany.
authors: Daniel
authors: D
authors: Weinbuch
authors: Jason K
authors: JK
authors: Cheung
authors: Jurgen
authors: J
authors: Ketelaars
authors: Vasco
authors: V
authors: Filipe
authors: Andrea
authors: A
authors: Hawe
authors: John
authors: J
authors: den Engelsman
authors: Wim
authors: W
authors: Jiskoot
mesh_terms: D001702:Biopharmaceutics / Q000379:methods* / Q000592:standards; D002241:Carbohydrates / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D004340:Drug Contamination / Q000517:prevention & control; D000067493:Dynamic Light Scattering; D008855:Microscopy, Electron, Scanning; D009113:Muramidase / Q000032:analysis*; D053758:Nanoparticles / Q000032:analysis*; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D014462:Ultrafiltration
chemical_list: D002241:Carbohydrates; D009113:Muramidase
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