Near-infrared imaging for high-throughput screening of moisture induced changes in freeze-dried formulations

Hjalte Trnka, Anna Palou, Pierre Emanuel Panouillot, Ari Kauppinen, Maunu Toiviainen, Holger Grohganz, Manel Alcalà, Mikko Juuti, Jarkko Ketolainen, Jukka Rantanen

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Evaluation of freeze-dried biopharmaceutical formulations requires careful analysis of multiple quality attributes. The aim of this study was to evaluate the use of near-infrared (NIR) imaging for fast analysis of water content and related physical properties in freeze-dried formulations. Model formulations were freeze-dried in well plates. Samples were imaged with a NIR hyperspectral camera after freeze-drying and upon storage. On the basis of Karl Fischer titration reference values, a univariate quantification model was constructed and used to visualize the distribution of water within freeze-dried samples. Differences observed between samples stored at 11% and 43% relative humidity (RH) were found to be related to the amount of amorphous component in the sample. When stored at 43% RH, the moisture content in samples with high sucrose content increased within 2 days and some degree of localized drying was observed within the samples after 3 days of storage. Further investigations with X-ray powder diffraction confirmed this local drying to be related to crystallization of sucrose. The combination of fast analysis of water content and spatial solid-state information makes NIR imaging a powerful tool for formulation development of freeze-dried samples. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.
Original languageEnglish
Pages (from-to)2839-2846
JournalJournal of Pharmaceutical Sciences
Issue number9
Publication statusPublished - 1 Jan 2014


  • formulation screening
  • freeze-drying
  • moisture
  • NIR imaging
  • solid state
  • sucrose crystallization
  • water-solid interactions


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