Zbacnik Teddy J, Holcomb Ryan E, Katayama Derrick S, Murphy Brian M, Payne Robert W, Coccaro Richard C, Evans Gabriel J, Matsuura James E, Henry Charles S, Manning Mark Cornell
LegacyBioDesign LLC, Johnstown, Colorado 80534.
LegacyBioDesign LLC, Johnstown, Colorado 80534; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523.
J Pharm Sci. 2017 Mar;106(3):713-733. doi: 10.1016/j.xphs.2016.11.014. Epub 2016 Nov 26.
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.
缓冲剂是蛋白质制剂不可或缺的组成部分。它们不仅能调节pH值的变化，还能通过多种机制稳定蛋白质。本综述重点介绍了缓冲剂在液态制剂、冷冻溶液或固态中稳定治疗性蛋白质的能力。缓冲剂的添加可提高蛋白质的构象稳定性，无论是通过配体结合还是通过排除溶质机制。此外，它们可以改变蛋白质的胶体稳定性并调节界面损伤。缓冲剂也可能导致蛋白质不稳定，并介绍了缓冲剂本身的稳定性。此外，还讨论了缓冲剂潜在的安全性和毒性问题，特别强调了缓冲剂对注射时痛感的影响。最后，研究了缓冲剂与其他辅料的相互作用。
