Thermal Gradient Mid- and Far-Infrared Spectroscopy as Tools for Characterization of Protein Carbohydrate Lyophilizates
American Chemical Society
MetadataShow full item record
Zeitler, A. (2017). Thermal Gradient Mid- and Far-Infrared Spectroscopy as Tools for Characterization of Protein Carbohydrate Lyophilizates. Molecular Pharmaceutics, 14 (10), 3550-3557. https://doi.org/10.1021/acs.molpharmaceut.7b00568
Protein drugs play an important role in modern day medicine. Typically, these proteins are formulated as liquids requiring cold chain processing. To circumvent the cold chain and achieve better storage stability, these proteins can be dried in the presence of carbohydrates. We demonstrate that thermal gradient mid- and far-infrared spectroscopy (FTIR and THz-TDS, respectively) can provide useful information about solid-state protein carbohydrate formulations regarding mobility and intermolecular interactions. A model protein (BSA) was lyophilized in the presence of three carbohydrates with different size and protein stabilizing capacity. A gradual increase in mobility was observed with increasing temperature in formulations containing protein and/or larger carbohydrates (oligo- or polysaccharides), lacking a clear onset of fast mobility as was observed for smaller molecules. Furthermore, both techniques are able to identify the glass transition temperatures (Tg) of the samples. FTIR provides additional information as it can independently monitor changes in protein and carbohydrate bands at the Tg. Lastly, THz-TDS confirms previous findings that protein–carbohydrate interactions decrease with increasing molecular weight of the carbohydrate, which results in decreased protein stabilization.
Fourier transform infrared spectroscopy (FTIR), hydrogen bonding, molecular mobility, solid state, terahertz time-domain spectroscopy (THz-TDS)
This research was jointly financed by Royal FrieslandCampina, the European Union, European Regional Development Fund and The Ministry of Economic Affairs, Agriculture and Innovation, Peaks in the Delta, the Municipality of Groningen, the Provinces of Groningen, Fryslân and Drenthe as well as the Dutch Carbohydrate Competence Center. Furthermore we acknowledge the support of the UK Engineering and Physical Sciences Research Council [EP/J007803/1].
External DOI: https://doi.org/10.1021/acs.molpharmaceut.7b00568
This record's URL: https://www.repository.cam.ac.uk/handle/1810/269521
Recommended or similar items
The following licence files are associated with this item: