Protein-Protein Interactions and Water Activity Coefficients can be used to aid a first Excipient Choice in Protein Formulations

Publication date: Available online 12 August 2019Source: International Journal of PharmaceuticsAuthor(s): Miko Schleinitz, Gabriele Sadowski, Christoph BrandenbuschAbstractWith respect to all biopharmaceuticals marketed to date, monoclonal antibodies represent the largest fraction with more than 48% market share (2012). However, the development of biopharmaceutical formulations is a challenging task, and time-consuming and cost-intensive high-throughput screenings are still state-of-the-art in formulation design. These screening techniques are almost exclusively based on heuristic decisions thus the benefit in terms of mechanistic understanding is often unclear. It requires novel, physical-sound methods to enhance/optimize future formulation development, ideally by understanding molecular interactions in these complex solutions. A suitable and evaluated measure-of-choice to characterize protein-protein interactions in aqueous protein solutions is the second osmotic virial coefficient B22 which can be measured using static light scattering techniques. Furthermore B22 can be modeled/predicted via the extended mxDLVO model for protein-protein interactions in the presence of single excipients and excipient-mixtures. Building up on this approach, giving an additional insight into water-water and water-excipient interactions, the thermodynamic equation-of-state ePC-SAFT is used to calculate water activity coefficients in the presence of excipient-mixtures. Immunoglobulin G (IgG) wa...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research