TY - JOUR
T1 - Chemical denaturation as a tool in the formulation optimization of biologics
AU - Freire, Ernesto
AU - Schön, Arne
AU - Hutchins, Burleigh M.
AU - Brown, Richard K.
N1 - Funding Information:
This work was supported by a grant from the National Institutes of Health R44 GM096751-02 .
PY - 2013/10
Y1 - 2013/10
N2 - Biologics have become the fastest growing segment in the pharmaceutical industry. As is the case with all proteins, biologics are susceptible to denature or to aggregate; conditions that, if present, preclude their use as pharmaceuticals. Identifying the solvent conditions that maximize their structural stability is crucial during development. Since the structural stability of a protein is susceptible to different chemical and physical conditions, the use of several complementary techniques can be expected to provide the best answers. Stability measurements that rely on temperature or chemical [urea or guanidine hydrochloride (GuHCl)] denaturation have been the preferred ones in research laboratories and together provide a thorough evaluation of protein stability. In this review, we will discuss chemical denaturation as a tool in the optimization of formulation conditions for biologics, and how chemical denaturation complements the role of thermal denaturation for this purpose.
AB - Biologics have become the fastest growing segment in the pharmaceutical industry. As is the case with all proteins, biologics are susceptible to denature or to aggregate; conditions that, if present, preclude their use as pharmaceuticals. Identifying the solvent conditions that maximize their structural stability is crucial during development. Since the structural stability of a protein is susceptible to different chemical and physical conditions, the use of several complementary techniques can be expected to provide the best answers. Stability measurements that rely on temperature or chemical [urea or guanidine hydrochloride (GuHCl)] denaturation have been the preferred ones in research laboratories and together provide a thorough evaluation of protein stability. In this review, we will discuss chemical denaturation as a tool in the optimization of formulation conditions for biologics, and how chemical denaturation complements the role of thermal denaturation for this purpose.
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U2 - 10.1016/j.drudis.2013.06.005
DO - 10.1016/j.drudis.2013.06.005
M3 - Review article
C2 - 23796912
AN - SCOPUS:84884592733
SN - 1359-6446
VL - 18
SP - 1007
EP - 1013
JO - Drug Discovery Today
JF - Drug Discovery Today
IS - 19-20
ER -