Synergistic Effects of Multiple Excipients on Controlling Viscosity of Concentrated Protein Dispersions |
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| Affiliation: | 1. School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, 510006, PR China;2. School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, PR China;3. College of Environmental and Chemical Engineering, Zhaoqing University, Zhaoqing, 526061, PR China;1. Department of Physics Chemistry and Pharmacy, University of Southern Denmark, Odense M, Denmark;2. Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Via San Donato 19/2, 40127 Bologna, Italy;1. Pharmaceutical Development, Genentech, 1 DNA Way, South San Francisco, CA, USA;2. Cell Culture and Bioprocess Operations, Genentech, 1 DNA Way, South San Francisco, CA, USA;3. Protein Chemistry, Genentech, 1 DNA Way, South San Francisco, CA, USA;4. Roche Diagnostics GmbH, Nonnenwald 2, 82377, Penzberg, Germany;1. Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD 20899, United States;2. Department of Drug Delivery and Device Development, Medimmune-AstraZeneca, Gaithersburg, MD 20878, United States |
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| Abstract: | Viscosity control is essential for the manufacturing and delivery of concentrated therapeutic proteins. Limited availability of the precious protein-based drugs hinders the characterization and screening of the formulation conditions with new types or different combinations of excipients. In this work, a droplet-based microfluidic device with incorporated multiple particle tracking microrheology (MPT) is developed to quantify the effects of two excipients, arginine hydrochloride (ArgHCl) and caffeine, on the viscosity of concentrated bovine gamma globulin (BGG) dispersions at two different values of pH. The effectiveness of both ArgHCl and caffeine show dependence on the BGG concentration and solution pH. The data set with high compositional resolution provides useful information to guide formulation with multiple viscosity-reducing excipients and quantification appropriate to start elucidating the connection to protein-protein interaction mechanisms. Overall, this work has demonstrated that the developed microfluidic approach has the potential to effectively assess the impact of multiple excipients on the viscosity and provide data for computational methods to predict viscosity for high concentration protein formulations. |
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