caa a22 4500 477127916 CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970501xx s 000 0 eng 10.1023/A:1012144810067 doi (NATIONALLICENCE)springer-10.1023/A:1012144810067 Effect of Glass Transition Temperature on the Stability of Lyophilized Formulations Containing a Chimeric Therapeutic Monoclonal Antibody [Elektronische Daten] [Sarma Duddu, Paul Dal Monte] Purpose. The purpose of this study is to highlight the importance of knowing the glass transition temperature, Tg, of a lyophilized amorphous solid composed primarily of a sugar and a protein in the interpretation of accelerated stability data. Methods. Glass transition temperatures were measured using DSC and dielectric relaxation spectroscopy. Aggregation of protein in the solid state was monitored using size-exclusion chromatography. Results. Sucrose formulation (Tg ~ 59°C) when stored at 60°C was found to undergo significant aggregation, while the trehalose formulation (Tg ~ 80°C) was stable at 60°C. The instability observed with sucrose formulation at 60°C can be attributed to its Tg (~59°C) being close to the testing temperature. Increase in the protein/sugar ratio was found to increase the Tgs of the formulations containing sucrose or trehalose, but to different degrees. Conclusions. Since the formulations exist in glassy state during their shelf-life, accelerated stability data generated in the glassy state (40°C) is perhaps a better predictor of the relative stability of formulations than the data generated at a higher temperature (60°C) where one formulation is in the glassy state while the other is near or above its Tg. Plenum Publishing Corporation, 1997 glass transition temperature Tg nationallicence lyophilization nationallicence solid-state stability nationallicence proteins nationallicence monoclonal antibody nationallicence aggregation nationallicence Duddu Sarma Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, 19406, Pennsylvania aut Dal Monte Paul Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, 19406, Pennsylvania aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 591-595 0724-8741 14:5<591 1997 14 11095 https://doi.org/10.1023/A:1012144810067 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012144810067 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Duddu Sarma Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, 19406, Pennsylvania aut NATIONALLICENCE 700 1- Dal Monte Paul Department of Pharmaceutical Technologies, SmithKline Beecham Pharmaceuticals, 19406, Pennsylvania aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 591-595 0724-8741 14:5<591 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer