Lyophilized protein formulations, molecular mobility

Duddu, S. ZJiang, G. Dal Monte, P. The relationship between protein aggregation and molecular mobility below the glass transition temperature of lyophilized formulations containing a monoclonal antibody. Pharm. Res. 1997, 14, 596-600. 

Yoshioka, S. Aso, Y. Kojima, S. Sakurai, S. Fujiwara, T. Akutsu, H. Molecular mobility of protein in lyophilized formulations linked to the molecular mobility of polymer excipients, as determined by high resolution C sohd-state NMR. Pharm. Res. 1999, id (10), 1621-1625. 

S. Yoshioka, Y. Aso, Y. Nakai, and S. Kojima, Effect of high molecular mobility of poly(vinyl alcohol) on protein stability of lyophilized y-globulin formulations, J. Pharm. Sci. 87, 147-151 (1998). 

As described above, the Ti of carbons in protein and excipient molecules can provide important information on the molecular mobility of lyophilized formulations. Similarly, the Ti, of carbons is useful as a measure of molecular mobility. Figure 16 shows the x of methine carbons in a lyophilized formulation containing dextran, calculated from the observed Tip according to equation (5). The x of methine carbon at 60%RH is of the same order as the x i of methine protons described in Section II.B. 

This chapter describes the dependence of the storage stability of lyophilized formulations on the molecular mobility as determined by NMR relaxation measurements, which was described in Section II, focusing on the degradation of small molecular weight drugs via bimolecular reaction and protein aggregation in lyophilized formulations. 

B. Effect of Molecular Mobility on Protein Aggregation during Storage of Lyophilized Formulations... 

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