(513g) Investigating Fundamental Motions to Rapidly Predict Lyophilized Protein Stability
AIChE Annual Meeting
2022
2022 Annual Meeting
Pharmaceutical Discovery, Development and Manufacturing Forum
Advances in New Modalities: Predictive Modeling Technologies
Wednesday, November 16, 2022 - 2:36pm to 2:57pm
It has been shown that there is a direct correlation between the degradation rate of proteins stored in the glass phase and molecular mobility of the systems in which the proteins are embedded1; this correlation holds true for a variety of proteins stored in multiple excipients and at multiple temperatures. This work was conducted using neutron scattering which is a technique less accessible to most researchers. However, alternative methods exist that allow for acquisition of similar data. The first method discussed in the present work is measurement of the optical Kerr effect (OKE) from which molecular reorientation times collected under the stress of an ultrashort laser pulse can be related to molecular mobility. It has been shown that measurement of the OKE provides signatures of the fundamental motions2, similar to observations from neutron scattering. The second method discussed in the present work is low-frequency Raman spectroscopy from which the energy difference of inelastically scattered light can be related to molecular mobility. Both these techniques are expected to provide insight on the stabilizing power of excipients in a much shorter window than current long-time studies because they measure the most fundamental motions of the system, which are sub-steps of the processes that cause protein degradation. These techniques can serve to drastically decrease the time spent optimizing formulations.
- Cicerone et al., Soft Matter, 8 (2012)
- Bender et al., Soft Matter, 16 (2020)