title: Specific decrease in solution viscosity of antibodies by arginine for therapeutic formulations.
abstract: Unacceptably high viscosity is observed in high protein concentration formulations due to extremely large therapeutic dose of antibodies and volume restriction of subcutaneous route of administration. Here, we show that a protein aggregation suppressor, arginine hydrochloride (ArgHCl), specifically decreases viscosity of antibody formulations. The viscosities of bovine gamma globulin (BGG) solution at 250 mg/mL and human gamma globulin (HGG) solution at 292 mg/mL at a physiological pH were too high for subcutaneous injections, but decreased to an acceptable level (below 50 cP) in the presence of 1,000 mM ArgHCl. ArgHCl also decreased the viscosity of BGG solution at acidic and alkaline pHs. Interestingly, ArgHCl decreased the viscosity of antibody solutions (BGG, HGG, and human immunoglobulin G) but not globular protein solutions (α-amylase and α-chymotrypsin). These results indicate not only high potency of ArgHCl as an excipient to decrease the solution viscosity of high concentration antibodies formulations but also specific interactions between ArgHCl and antibodies.
authors.affiliation: Faculty of Pure and Applied Sciences, University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Inoue
authors.forename: Eisuke
authors.initials: E
authors.lastname: Takai
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Arakawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry*; D001120:Arginine / Q000737:chemistry*; D002417:Cattle; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002918:Chymotrypsin / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000737:chemistry; D066329:Protein Aggregates / Q000187:drug effects; D012996:Solutions / Q000737:chemistry*; D014783:Viscosity / Q000187:drug effects*; D000516:alpha-Amylases / Q000737:chemistry; D005719:gamma-Globulins / Q000737:chemistry
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D066329:Protein Aggregates; D012996:Solutions; D005719:gamma-Globulins; D001120:Arginine; D000516:alpha-Amylases; D002918:Chymotrypsin; C117608:alpha-chymotrypsin