Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Zeitler, JA 

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.

Description

Keywords

Fourier transform infrared spectroscopy (FTIR), hydrogen bonding, molecular mobility, solid state, terahertz time-domain spectroscopy (THz-TDS)

Journal Title

Molecular Pharmaceutics

Conference Name

Journal ISSN

1543-8384
1543-8392

Volume Title

14

Publisher

American Chemical Society
Sponsorship
Engineering and Physical Sciences Research Council (EP/J007803/1)
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].