Local Mobility and Degree of Retention of Native Secondary Structure Contribute to the Stability of Recombinant Human Growth Hormone in Glassy Lyophilized Formulations

Using recombinant human growth hormone (rhGH)  as a model, we created a variety of glassy, lyophilized formulations and studied how degradation rates depended on the the degree of retention of protein secondary structure and on glassy-state  mobilities.    Secondary structures were detrmined from solid-state FTIR analysis of amideI bands; local and global mobilities were determined by neutron scattering and calorimetry, respectively.  Rate constants for degradation (aggregation, deamidation, and oxidation) strongly correlated with both protein structure and local mobility in the glass.   Degradation rate constants were inversely correlated with global mobility, as  quantified by proximity to glass transition temperatures and by entalpy relaxation measurements .