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Thermal Gradient Mid- and Far-Infrared Spectroscopy as Tools for Characterization of Protein Carbohydrate Lyophilizates

Mensink, M. A., S ̌ib í k, J., Frijlink, H. W., Maarschalk, K. V. D. V., Hinrichs, W. L. J. & Zeitler, J. A., Oct-2017, In : Molecular pharmaceutics. 14, 10, p. 3550-3557 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

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 (T-g) of the samples. FTIR provides additional information as it can independently monitor changes in protein and carbohydrate bands at the T-g. Lastly, THz-TDS confirms previous findings that protein-carbohydrate interactions decrease with increasing molecular weight of the carbohydrate, which results in decreased protein stabilization.

Original languageEnglish
Pages (from-to)3550-3557
Number of pages8
JournalMolecular pharmaceutics
Volume14
Issue number10
Publication statusPublished - Oct-2017

    Keywords

  • terahertz time-domain spectroscopy (THz-TDS), Fourier transform infrared spectroscopy (FTIR), hydrogen bonding, molecular mobility, solid state, TERAHERTZ TIME-DOMAIN, STORAGE STABILITY, GLASSY STATE, SOLID-STATE, DYNAMICS, SUGAR, PHARMACEUTICALS, STABILIZATION, RELAXATION, MECHANISMS

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