Mariya A Pindrus1, Steven J Shire2, Sandeep Yadav2, Devendra S Kalonia1. 1. Department of Pharmaceutical Sciences , University of Connecticut , U-3092, Storrs , Connecticut 06269 , United States. 2. Late Stage Pharmaceutical Development , Genentech, Inc ., 1 DNA Way , South San Francisco , California 94080 , United States.
Abstract
PURPOSE: To determine the effect of solution conditions, especially low ionic strength, on the dynamics of molecular diffusion and protein-protein interactions in monoclonal antibody solutions. METHODS: The interaction parameter, kD, was calculated from diffusion data obtained from dynamic light scattering (DLS) measurements performed using a Zetasizer. Theoretical considerations were utilized to evaluate the hard sphere and electrostatic contribution to molecular interactions. RESULTS: At low ionic strengths, repulsions were the dominant forces governing the behavior of both mAbs. As ionic strength increased, attractions contributed to the behavior of mAb1, while repulsions remained the dominant factor affecting mAb3 behavior. Repulsions alone were not sufficient to affect mAb3 viscosity in water, while the presence of repulsions as well as specific attractions was suggested to cause an increase in the viscosity of mAb1 in water compared to 15 mM ionic strength. CONCLUSIONS: Solution physical properties varied for the mAbs investigated. Our findings highlighted the importance of developing a fundamental understanding of interplay of forces governing solution properties of each individual mAb under low ionic strength conditions. Such understanding is critical in enabling successful development of self-buffered formulations.
PURPOSE: To determine the effect of solution conditions, especially low ionic strength, on the dynamics of molecular diffusion and protein-protein interactions in monoclonal antibody solutions. METHODS: The interaction parameter, kD, was calculated from diffusion data obtained from dynamic light scattering (DLS) measurements performed using a Zetasizer. Theoretical considerations were utilized to evaluate the hard sphere and electrostatic contribution to molecular interactions. RESULTS: At low ionic strengths, repulsions were the dominant forces governing the behavior of both mAbs. As ionic strength increased, attractions contributed to the behavior of mAb1, while repulsions remained the dominant factor affecting mAb3 behavior. Repulsions alone were not sufficient to affect mAb3 viscosity in water, while the presence of repulsions as well as specific attractions was suggested to cause an increase in the viscosity of mAb1 in water compared to 15 mM ionic strength. CONCLUSIONS: Solution physical properties varied for the mAbs investigated. Our findings highlighted the importance of developing a fundamental understanding of interplay of forces governing solution properties of each individual mAb under low ionic strength conditions. Such understanding is critical in enabling successful development of self-buffered formulations.
Authors: Sarah Molokhia; Kongnara Papangkorn; Charlotte Butler; John W Higuchi; Balbir Brar; Balamurali Ambati; S Kevin Li; William I Higuchi Journal: J Ocul Pharmacol Ther Date: 2020-03-05 Impact factor: 2.671
Authors: Oliver Bluemel; Jakob W Buecheler; Astrid Hauptmann; Georg Hoelzl; Karoline Bechtold-Peters; Wolfgang Friess Journal: Int J Pharm X Date: 2021-12-25