title: Interactions of formulation excipients with proteins in solution and in the dried state.
abstract: A variety of excipients are used to stabilize proteins, suppress protein aggregation, reduce surface adsorption, or to simply provide physiological osmolality. The stabilizers encompass a wide variety of molecules including sugars, salts, polymers, surfactants, and amino acids, in particular arginine. The effects of these excipients on protein stability in solution are mainly caused by their interaction with the protein and the container surface, and most importantly with water. Some excipients stabilize proteins in solution by direct binding, while others use a number of fundamentally different mechanisms that involve indirect interactions. In the dry state, any effects that the excipients confer to proteins through their interactions with water are irrelevant, as water is no longer present. Rather, the excipients stabilize proteins through direct binding and their effects on the physical properties of the dried powder. This review will describe a number of mechanisms by which the excipients interact with proteins in solution and with various interfaces, and their effects on the physical properties of the dried protein structure, and explain how the various interaction forces are related to their observed effects on protein stability.
authors.affiliation: Aridis Pharmaceuticals, 5941 Optical Court, San Jose, CA 95138, USA.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtake
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kita
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Arakawa
mesh_terms: D001120:Arginine / Q000737:chemistry; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D006801:Humans; D011108:Polymers / Q000737:chemistry*; D011208:Powders; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012996:Solutions; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D005079:Excipients; D011108:Polymers; D011208:Powders; D011506:Proteins; D012996:Solutions; D013501:Surface-Active Agents; D001120:Arginine