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Keywords:

  • protein aggregation;
  • biopharmaceuticals characterization;
  • protein formulation;
  • image analysis;
  • microparticles;
  • nanoparticles;
  • particle size;
  • proteins;
  • analysis

Abstract

Our study aimed to comparatively evaluate Micro–Flow Imaging (MFI) and the recently introduced technique of resonant mass measurement (Archimedes, RMM) as orthogonal methods for the quantitative differentiation of silicone oil droplets and protein particles. This distinction in the submicron and micron size range is highly relevant for the development of biopharmaceuticals, in particular for products in prefilled syringes. Samples of artificially generated silicone oil droplets and protein particles were quantified individually and in defined mixtures to assess the performance of the two techniques. The built-in MFI software solution proved to be suitable to discriminate between droplets and particles for sizes above 2 μm at moderate droplet/particle ratios (70:30–30:70). A customized filter developed specifically for this study greatly improved the results and enabled reliable discrimination also for more extreme mixing ratios (95:5–15:85). RMM showed highly accurate discrimination in the size range of about 0.5–2 μm independent of the ratio, provided that a sufficient number of particles (>50 counted particles) were counted. We recommend applying both techniques for a comprehensive analysis of biotherapeutics potentially containing silicone oil droplets and protein particles in the submicron and micron size range. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2152–2165, 2013