Effect of high molecular mobility of poly(vinyl alcohol) on protein stability of lyophilized gamma-globulin formulations.

The protein stability of lyophilized serum gamma-globulin (BGG) formulations containing poly(vinyl alcohol) (PVA) and dextran was studied in relation to the molecular mobility as determined by proton NMR. The critical temperature, Tmc, at which the Lorentzian relaxation process due to liquid polymer protons appears in these lyophilized formulations was lower than the glass transition temperature, Tg. Above Tmc, protein aggregation in the formulations was related to the Tmc according to the Williams-Landel-Ferry equation by replacing Tg with Tmc. Protein aggregation appears to occur substantially in a "rubbery-like" state even below Tg, if the formulations become microscopically liquidized above Tmc. Lyophilized BGG formulations containing PVA with a lower water content were less stable than those containing dextran with a higher water content. The difference in stability can be explained by the difference in the Tmc of these formulations. Tmc that is determined by NMR relaxation measurement appears to be a useful parameter for the characterization of protein formulations, for which the Tg cannot generally be determined by standard calorimetric techniques. Furthermore, Tmc appears to be more closely related to protein stability than does Tg.