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.
['Trnka|Hjalte|H|', 'Palou|Anna|A|', 'Panouillot|Pierre Emanuel|PE|', 'Kauppinen|Ari|A|', 'Toiviainen|Maunu|M|', 'Grohganz|Holger|H|', 'Alcalà|Manel|M|', 'Juuti|Mikko|M|', 'Ketolainen|Jarkko|J|', 'Rantanen|Jukka|J|']
D002626:Chemistry, Pharmaceutical D003460:Crystallization D003890:Desiccation D005612:Freeze Drying D006813:Humidity D004364:Pharmaceutical Preparations D011208:Powders D019265:Spectroscopy, Near-Infrared D013395:Sucrose D014867:Water D014961:X-Ray Diffraction
moisture freeze-drying NIR imaging formulation screening solid state sucrose crystallization water-solid interactions