Abstract
Incorporation of therapeutic proteins in a matrix of sugar glass is known to enhance protein stability, yet protection is often lost when exposed to high relative humidity (RH). We hypothesized that especially in these conditions the use of binary glasses of a polysaccharide and disaccharide might yield advantages for protein stability. Therefore, different amounts of the polysaccharide pullulan were introduced in freeze-dried trehalose glasses. In these homogeneous blends, the presence of pullulan above 50 weight % prevented crystallization of trehalose when exposed to high RH. Storage stability testing up to 4 weeks of the model protein β-galactosidase incorporated in pullulan/trehalose blends showed superior behavior of pure trehalose at 30°C/0% RH, while pullulan/trehalose blends yielded the best stability at 30°C/56% RH. In conclusion, binary glasses of pullulan and trehalose may provide excellent stability of proteins under storage conditions that may occur in practice, namely high temperature and high RH.
Highlights
Proteins are becoming an increasingly relevant class of drugs in today’s pharmacotherapy
Our results show that pullulan has some advantageous properties for protein stabilization, most importantly its very high glass transition temperature (Tg) which amply remains above room temperature even when exposed to high relative humidity (RH)
Since pullulan is a bulky molecule, it may not be able to provide for an optimal molecular packing around proteins, preventing optimal local vitrification and water replacement (Mensink et al, 2017), despite the benefits of its high Tg
Summary
Proteins are becoming an increasingly relevant class of drugs in today’s pharmacotherapy. Due to their size as well as their complex and labile structure, ensuring stability of therapeutic proteins requires a completely different formulation approach than for conventional small molecule drugs (Manning, Chou, Murphy, Payne, & Katayama, 2010; Mitragotri, Burke, & Langer, 2014). In case of impaired stability of proteins, their efficacy may be reduced, but degradation products may elicit undesired immune reactions, with serious consequences for the patient (Jiskoot et al, 2012; Ratanji et al, 2014). By storing proteins in the dry state, the degradation rate may be drastically reduced due to limited molecular mobility (Lai & Topp, 1999). Appropriate protection of the protein against such stresses, during both manufacturing and storage, is necessary
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
