(553f) Investigating Fundamental Motions for Rapid Screening of Lyophilized Protein Stability | AIChE

(553f) Investigating Fundamental Motions for Rapid Screening of Lyophilized Protein Stability


Badilla, K. - Presenter, University of South Alabama
Bommarius, A., Georgia Institute of Technology
Cicerone, M. T., National Institute of Standards and Technology
Protein-based therapeutic drugs have served an important role in the treatment of several conditions, including cancers and diabetes. Preservation of these proteins is critical for the safety and efficacy of these drugs, as well as their distribution. Lyophilization (freeze-drying) has proved to be an effective technique for extending the shelf-life and decreasing the dependence of the cold chain for protein-based drugs, and careful consideration of excipient can further increase stability. While it is obviously advantageous that lyophilized formulations are more stable, longer degradation times can result in longer studies (and more resources) to determine degradation rates and determine which excipients are better or worse at stabilizing the protein. The objective of this work is to demonstrate that by characterizing the short timescale motions of the lyophilized system, stability prediction times can decrease from year-long to minutes.

In 2012, Cicerone1 showed that that there is a direct relationship between the degradation rates of several lyophilized proteins and the mobility of the systems in which they are embedded; this work included proteins that spanned an order of magnitude in their molecular weights, stored in different excipients at different temperatures. However, this data was attained with neutron scattering, a generally inaccessible technique to those both in academia or industry. Similarly, the presented work utilizes label-free, non-destructive methods of obtaining similar information as with neutron scattering, but with optical techniques that are much more accessible. With corroboration from frequently utilized protein-characterization techniques such as nano-differential scanning fluorimetry, circular dichroism, and dynamic light scattering, we demonstrate that the time spent performing lyophilized protein stability screening can be greatly reduced from a year or more to minutes. The work includes proteins such as alcohol dehydrogenase (ADH), horseradish peroxidase (HRP), as well as IgG1.

1. Cicerone et al., Soft Matter, 8 (2012)