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

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 J Pharm Sci 103:2839–2846, 2014