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Micro–flow imaging and resonant mass measurement (archimedes) – complementary methods to quantitatively differentiate protein particles and silicone oil droplets

Authors

  • Daniel Weinbuch,

    1. Coriolis Pharma, Am Klopferspitz 19, 82152 Martinsried-Munich, Germany
    2. Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300RA Leiden, The Netherlands
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    • Daniel Weinbuch and Sarah Zölls are joint first authors.

  • Sarah Zölls,

    1. Coriolis Pharma, Am Klopferspitz 19, 82152 Martinsried-Munich, Germany
    2. Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilian University, Munich 81377, Germany
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    • Daniel Weinbuch and Sarah Zölls are joint first authors.

  • Michael Wiggenhorn,

    1. Coriolis Pharma, Am Klopferspitz 19, 82152 Martinsried-Munich, Germany
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  • Wolfgang Friess,

    1. Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilian University, Munich 81377, Germany
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  • Gerhard Winter,

    1. Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig Maximilian University, Munich 81377, Germany
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  • Wim Jiskoot,

    1. Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, P.O. Box 9502, 2300RA Leiden, The Netherlands
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  • Andrea Hawe

    Corresponding author
    1. Coriolis Pharma, Am Klopferspitz 19, 82152 Martinsried-Munich, Germany
    • Coriolis Pharma, Am Klopferspitz 19, 82152 Martinsried-Munich, Germany. Telephone: +49-89542449825; Fax: +49-89542449822
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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

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