Preservation of therapeutic-protein formulations is critical for patient safety and treatment efficacy and while lyophilization (freeze-drying) has been shown as an effective technique for enhancing the longevity of proteins in these products, degradation is often still imminent. To determine the timescale of the degradation processes in these lyophilized systems, time-point studies on the order of >1 year are required which can be resource intensive if there are several candidates for the formulation. In this work, I will demonstrate novel-to-application optical techniques that can provide the insight required to accelerate lyophilized protein-based drug formulation development.
A previous publication (MT Cicerone et al., Soft Matter 2012) provided evidence for a relationship between the degradation rates of several lyophilized proteins and the dynamics of the excipients that the proteins were lyophilized in. There are several works by others that investigate system dynamics through viscosity and glass-transition temperature, but to this end, show no clear correlation with stability. The publication by Cicerone, however, looked at more fundamental motions of the excipients: individual molecules hopping over each other. This data was acquired with neutron scattering, a technique less accessible to academia and industry, so the present work explores optical techniques to acquire similar data.
In this study, stability of lyophilized horseradish peroxidase (HRP) is characterized with enzymatic assays. This data is then compared to the optical techniques which provide information regarding quantity of fundamental motions of the system (less motion means more stable protein). As these optical methods take on the order of minutes, with this work, we approach a promising method to reduce lyophilized protein formulation development times from a year to minutes.
