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Keywords:

  • particle sizing;
  • image analysis;
  • imaging methods;
  • proteins;
  • physical characterization;
  • microflow imaging;
  • receiver operating characteristic;
  • medium test dust

Abstract

New methods are being applied to distinguish silicone oil droplets from subvisible particles in therapeutic protein formulations. The need to standardize these methods and compare them to established methods is critical to increase the understanding of the risks from protein aggregation and other subvisible particulate matter. We present the use of medium test dust (MTD) as a stable subvisible particle standard that can be distinguished from silicone oil by flow imaging methodology and the combination of light obscuration and microscopic methods. We further present the use of binary classification techniques to characterize the ability of flow imaging to distinguish between particle types (i.e., silicone vs. protein, silicone vs. standard, etc.) as a function of particle size. For the differentiation of silicone oil and MTD, the aspect ratio attribute was as good as or better than any other characteristic or combination of two characteristics applied to distinguish this particle population. However, the value of the discrimination by flow imaging was limited to particles larger than 5 μm. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1696–1700, 2013