Abstract:
: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.
journal_name
Mol Pharmjournal_title
Molecular pharmaceuticsauthors
Mensink MA,Šibík J,Frijlink HW,van der Voort Maarschalk K,Hinrichs WLJ,Zeitler JAdoi
10.1021/acs.molpharmaceut.7b00568subject
Has Abstractpub_date
2017-10-02 00:00:00pages
3550-3557issue
10eissn
1543-8384issn
1543-8392journal_volume
14pub_type
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