caa a22 4500 477127967 CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970501xx s 000 0 eng 10.1023/A:1012196826905 doi (NATIONALLICENCE)springer-10.1023/A:1012196826905 The Relationship Between Protein Aggregation and Molecular Mobility Below the Glass Transition Temperature of Lyophilized Formulations Containing a Monoclonal Antibody [Elektronische Daten] [Sarma Duddu, Guangzhong Zhang, Paul Dal Monte] Purpose. To find out if the physical instability of a lyophilized dosage form is related to molecular mobility below the glass transition temperature. Further, to explore if the stability data generated at temperatures below the glass transition temperature can be used to predict the stability of a lyophilized solid under recommended storage conditions. Methods. The temperature dependence of relaxation time constant, τ, was obtained for sucrose and trehalose formulations of the monoclonal antibody (5 mg protein/vial) from enthalpy relaxation studies using differential scanning calorimetry. The non-exponentiality parameter, β, in the relaxation behavior was also obtained using dielectric relaxation spectroscopy. Results. For both sucrose and trehalose formulations, the variation in τ with temperature could be fitted Vogel-Tammann-Fulcher (VTF) equation. The two formulations exhibited difference sensitivities to temperature. Sucrose formulation was more fragile and exhibited a stronger non-Arrhenius behavior compared to trehalose formulation below glass transition. Both formulations exhibited <2% aggregation at tτ values <10, where t is the time of storage. Conclusions. Since the relaxation times for sucrose and trehalose formulations at 5°C are on the order of 108 and 106 hrs, it is likely that both formulations would undergo very little (<2%) aggregation in a practical time scale under refrigerated conditions. Plenum Publishing Corporation, 1997 sucrose nationallicence trehalose nationallicence molecular mobility below glass transition nationallicence protein aggregation nationallicence Vogel-Tammann-Fulcher (VTF) equation nationallicence fragility of glasses nationallicence Duddu Sarma Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, 19406, King of Prussia, Pennsylvania aut Zhang Guangzhong Summer Intern from the Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 55455, Minneapolis, Minnesota aut Dal Monte Paul Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, 19406, King of Prussia, Pennsylvania aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 596-600 0724-8741 14:5<596 1997 14 11095 https://doi.org/10.1023/A:1012196826905 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012196826905 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Duddu Sarma Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, 19406, King of Prussia, Pennsylvania aut NATIONALLICENCE 700 1- Zhang Guangzhong Summer Intern from the Department of Pharmaceutics, College of Pharmacy, University of Minnesota, 55455, Minneapolis, Minnesota aut NATIONALLICENCE 700 1- Dal Monte Paul Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, 19406, King of Prussia, Pennsylvania aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 596-600 0724-8741 14:5<596 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer