caa a22 4500 445312238 CHVBK 20180317142634.0 cr unu---uuuuu 170323e20110701xx s 000 0 eng 10.1007/s11095-011-0388-7 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0388-7 Effect of Sugar Molecules on the Viscosity of High Concentration Monoclonal Antibody Solutions [Elektronische Daten] [Feng He, Christopher Woods, Jennifer Litowski, Lauren Roschen, Himanshu Gadgil, Vladimir Razinkov, Bruce Kerwin] ABSTRACT: Purpose: To assess the effect of sugar molecules on solution viscosity at high protein concentrations. Methods: A high throughput dynamic light scattering method was used to measure the viscosity of monoclonal antibody solutions. The effects of protein concentration, type of sugar molecule (trehalose, sucrose, sorbitol, glucose, fructose, xylose and galactose), temperature and ionic strength were evaluated. Differential scanning fluorimetry was used to reveal the effect of the same sugars on protein stability and to provide insight into the mechanism by which sugars increase viscosity. Results: The addition of all seven types of sugar molecules studied result in a significant increase in viscosity of high concentration monoclonal antibody solutions. Similar effects of sugars were observed in the two mAbs examined; viscosity could be reduced by increasing the ionic strength or temperature. The effect by sugars was enhanced at higher protein concentrations. Conclusions: Disaccharides have a greater effect on the solution viscosity at high protein concentrations compared to monosaccharides. The effect may be explained by commonly accepted mechanisms of interactions between sugar and protein molecules in solution. Springer Science+Business Media, LLC, 2011 dynamic light scattering nationallicence high throughput nationallicence monoclonal antibody nationallicence preferential exclusion nationallicence preferential hydration nationallicence sugar molecule nationallicence viscosity nationallicence cP : centipoise nationallicence DLS : dynamic light scattering nationallicence DSF : differential scanning fluorimetry nationallicence Igg : Immunoglobulin G nationallicence mAb : monoclonal antibody nationallicence He Feng Formulation and Analytical Resources, Amgen, Inc., Seattle, Washington, USA aut Woods Christopher Formulation and Analytical Resources, Amgen, Inc., Seattle, Washington, USA aut Litowski Jennifer Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA aut Roschen Lauren Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA aut Gadgil Himanshu Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA aut Razinkov Vladimir Formulation and Analytical Resources, Amgen, Inc., Seattle, Washington, USA aut Kerwin Bruce Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1552-1560 0724-8741 28:7<1552 2011 28 11095 https://doi.org/10.1007/s11095-011-0388-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0388-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- He Feng Formulation and Analytical Resources, Amgen, Inc., Seattle, Washington, USA aut NATIONALLICENCE 700 1- Woods Christopher Formulation and Analytical Resources, Amgen, Inc., Seattle, Washington, USA aut NATIONALLICENCE 700 1- Litowski Jennifer Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA aut NATIONALLICENCE 700 1- Roschen Lauren Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA aut NATIONALLICENCE 700 1- Gadgil Himanshu Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA aut NATIONALLICENCE 700 1- Razinkov Vladimir Formulation and Analytical Resources, Amgen, Inc., Seattle, Washington, USA aut NATIONALLICENCE 700 1- Kerwin Bruce Analytical and Formulation Sciences, Amgen, Inc., Seattle, Washington, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/7(2011-07-01), 1552-1560 0724-8741 28:7<1552 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer