title: Near-infrared imaging for high-throughput screening of moisture induced changes in freeze-dried formulations.
abstract: 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.
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, 2100, Denmark.
authors.forename: Hjalte
authors.initials: H
authors.lastname: Trnka
authors.affiliation: Applied Chemometrics Group, Analytical Chemistry Unit, Department of Chemistry, Faculty of Sciences, Universitat Autònoma de Barcelona 01893, Bellaterra, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Palou
authors.affiliation: Optical Measurement Technologies, VTT Technical Research Centre of Finland, Kuopio, FI 70211, Finland.
authors.forename: Pierre Emanuel
authors.initials: PE
authors.lastname: Panouillot
authors.affiliation: School of Pharmacy, Promis Centre, Faculty of Health Sciences, University of Eastern Finland, Kuopio, FI 70211, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Kauppinen
authors.affiliation: Optical Measurement Technologies, VTT Technical Research Centre of Finland, Kuopio, FI 70211, Finland.
authors.forename: Maunu
authors.initials: M
authors.lastname: Toiviainen
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, 2100, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Grohganz
authors.affiliation: Applied Chemometrics Group, Analytical Chemistry Unit, Department of Chemistry, Faculty of Sciences, Universitat Autònoma de Barcelona 01893, Bellaterra, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Alcalà
authors.affiliation: Optical Measurement Technologies, VTT Technical Research Centre of Finland, Kuopio, FI 70211, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Juuti
authors.affiliation: School of Pharmacy, Promis Centre, Faculty of Health Sciences, University of Eastern Finland, Kuopio, FI 70211, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Ketolainen
authors.affiliation: Department of Pharmacy, University of Copenhagen, Copenhagen, 2100, Denmark. Electronic address: jukka.rantanen@sund.ku.dk.
authors.forename: Jukka
authors.initials: J
authors.lastname: Rantanen
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization / Q000379:methods; D003890:Desiccation / Q000379:methods; D005612:Freeze Drying / Q000379:methods; D006813:Humidity; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013395:Sucrose / Q000737:chemistry; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders; D014867:Water; D013395:Sucrose
keywords: NIR imaging; formulation screening; freeze-drying; moisture; solid state; sucrose crystallization; water-solid interactions