title: Role of Buffers in Protein Formulations.
abstract: Buffers comprise an integral component of protein formulations. Not only do they function to regulate shifts in pH, they also can stabilize proteins by a variety of mechanisms. The ability of buffers to stabilize therapeutic proteins whether in liquid formulations, frozen solutions, or the solid state is highlighted in this review. Addition of buffers can result in increased conformational stability of proteins, whether by ligand binding or by an excluded solute mechanism. In addition, they can alter the colloidal stability of proteins and modulate interfacial damage. Buffers can also lead to destabilization of proteins, and the stability of buffers themselves is presented. Furthermore, the potential safety and toxicity issues of buffers are discussed, with a special emphasis on the influence of buffers on the perceived pain upon injection. Finally, the interaction of buffers with other excipients is examined.
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534.
authors.forename: Teddy J
authors.initials: TJ
authors.lastname: Zbacnik
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Ryan E
authors.initials: RE
authors.lastname: Holcomb
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Derrick S
authors.initials: DS
authors.lastname: Katayama
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Murphy
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Payne
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Coccaro
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534.
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Evans
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534.
authors.forename: James E
authors.initials: JE
authors.lastname: Matsuura
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523.
authors.forename: Charles S
authors.initials: CS
authors.lastname: Henry
authors.affiliation: LegacyBioDesign LLC, Johnstown, Colorado 80534; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523. Electronic address: Manning@LegacyBioDesign.com.
authors.forename: Mark Cornell
authors.initials: MC
authors.lastname: Manning
mesh_terms: D002021:Buffers; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002021:Buffers; D005079:Excipients; D011506:Proteins
keywords: chemical stability; excipients; physical stability; physicochemical properties; protein formulation; stabilization