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Application Of Infrared Spectroscopy To Development Of Stable Lyophilized Protein Formulations.

J. Carpenter, S. Prestrelski, A. Dong
Published 1998 · Chemistry, Medicine

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The preparation of protein therapeutics as lyophilized (freeze-dried) products is often essential to obtain the requisite stability during shipping and long-term storage. When prepared properly, lyophilized proteins can retain stability for months or even years at ambient temperature [1]. A crucial aspect of proper, rational development of a lyophilized formulation is the recognition that the most sensitive element in the system is the protein itself. Unfortunately, in the early days of preparing lyophilized protein formulations, it appears that frequently the focus was primarily on obtaining an acceptable dried cake structure, with the apparent assumption that a protein would be resistant to freezing and dehydration stresses. For example, when only mannitol is employed as an excipient and crystalline bulking agent, the resulting cake structure is usually excellent, but proteins derive essentially no protection from crystalline mannitol [1]. Such approaches, which can be sufficient for more stable low molecular weight drugs, led to dried products in which the protein was so susceptible to physical and/ or chemical degradation that shipping and storage at subzero temperatures was required. Obviously, the potential advantages of a lyophilized product are mostly lost when there are such stringent requirements for control of product temperature. It is now well known that without adequate stabilization by the appropriate amorphous excipients (e.g. sucrose), the protein can be irreversibly denatured after lyophilization and reconstitution and/or after long-term storage in the dried solid and rehydration [1–8]. Since most protein drugs are delivered parenterally, even if only a small fraction of the total protein molecular population (e.g. a few percent) is irreversibly denatured and aggregated, then the product will not be acceptable. Until recently the changes in protein structure arising during the processing steps of lyophilization, which were usually manifested as protein aggregation after rehydration, were unknown. However, with infrared spectroscopy it is now possible to examine directly the secondary structure of a protein in the initial aqueous solution, and in both the frozen state and the final dried solid. This analysis, combined with exploitation of stabilizers that are specific for either freezing or drying stresses, has documented that both freezing and dehydration can induce protein unfolding [1–8]. Unfolding not only can lead to irreversible protein denaturation, if the sample is rehydrated immediately, but, perhaps more importantly for industrial development of lyophilized protein drugs, can also reduce storage stability in the dried solid [1,6,7]. Moreover, simply obtaining a native protein in samples rehydrated immediately after lyophilization is not necessaEuropean Journal of Pharmaceutics and Biopharmaceutics 45 (1998) 231–238
This paper references
10.1021/JS960019T
Effects of phase separating systems on lyophilized hemoglobin.
M. Heller (1996)
10.1016/S0065-3233(08)60232-6
Hydration of proteins and polypeptides.
I. Kuntz (1974)
10.1002/BIP.360250307
Examination of the secondary structure of proteins by deconvolved FTIR spectra
D. Byler (1986)
10.1016/S0006-3495(93)81120-2
Dehydration-induced conformational transitions in proteins and their inhibition by stabilizers.
S. Prestrelski (1993)
10.1023/A:1016296801447
Optimization of Lyophilization Conditions for Recombinant Human Interleukin-2 by Dried-State Conformational Analysis Using Fourier-Transform Infrared Spectroscopy
S. Prestrelski (2004)
10.1016/0076-6879(86)30015-6
Resolution-enhanced Fourier transform infrared spectroscopy of enzymes.
H. Susi (1986)
10.1006/ABBI.1993.1309
Separation of freezing- and drying-induced denaturation of lyophilized proteins using stress-specific stabilization. I. Enzyme activity and calorimetric studies.
J. Carpenter (1993)
10.1016/S0065-3233(08)60528-8
Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins.
S. Krimm (1986)
10.1006/ABBI.1996.0305
Physical factors affecting the storage stability of freeze-dried interleukin-1 receptor antagonist: glass transition and protein conformation.
B. Chang (1996)
10.1016/S0006-3495(96)79400-6
Counteracting effects of thiocyanate and sucrose on chymotrypsinogen secondary structure and aggregation during freezing, drying, and rehydration.
S. D. Allison (1996)
10.1016/0378-5173(91)90075-Y
The effects of additives on the stability of freeze-dried β-galactosidase stored at elevated temperature
Izutsu Ken-ichi (1991)
10.1021/BI9518104
Infrared and circular dichroism spectroscopic characterization of structural differences between beta-lactoglobulin A and B.
A. Dong (1996)
10.1002/JPS.2600840407
Infrared spectroscopic studies of lyophilization- and temperature-induced protein aggregation.
A. Dong (1995)
10.1002/CHIN.199504319
Structure of Proteins in Lyophilized Formulations Using Fourier Transform Infrared Spectroscopy.
S. Prestrelski (1995)
10.1016/0167-4838(88)90107-0
New insight into protein secondary structure from resolution-enhanced infrared spectra.
W. Surewicz (1988)
10.1016/0065-227X(83)90008-4
Water and proteins. II. The location and dynamics of water in protein systems and its relation to their stability and properties.
J. Edsall (1983)
10.1016/S0065-3233(08)60197-7
Protein hydration and function.
J. Rupley (1991)
10.1021/JS950332F
Quantitation of the area of overlap between second-derivative amide I infrared spectra to determine the structural similarity of a protein in different states.
B. Kendrick (1996)
10.1006/ABBI.1993.1310
Separation of freezing- and drying-induced denaturation of lyophilized proteins using stress-specific stabilization. II. Structural studies using infrared spectroscopy.
S. Prestrelski (1993)
10.1126/science.267.5206.1924
Formation of Glasses from Liquids and Biopolymers
C. Angell (1995)
Infrared spectroscopy of biomolecules
H. Mantsch (1996)
10.1016/0076-6879(94)32047-0
Infrared methods for study of hemoglobin reactions and structures.
A. Dong (1994)



This paper is referenced by
10.1016/S0378-5173(00)00423-3
Lyophilization and development of solid protein pharmaceuticals.
W. Wang (2000)
10.1016/J.EJPB.2006.07.002
Trehalose and hyaluronic acid coordinately stabilized freeze-dried pancreatic kininogenase.
Y. Zhang (2007)
10.1080/07373937.2020.1806863
High molecular weight chitosan based particles for insulin encapsulation obtained via nanospray technology
Cecilia Prudkin-Silva (2020)
10.1002/9780470595886.CH37
Impact of Manufacturing Processes on Drug Product Stability and Quality
N. Rathore (2010)
10.1385/1-59259-922-2:243
Principles of Biopharmaceutical Protein Formulation
S. Sellers (2005)
Understanding Lyophilization Formulation
F. Bedu-Addo (2004)
10.1016/J.AB.2007.03.041
Characterizing protein structure in amorphous solids using hydrogen/deuterium exchange with mass spectrometry.
Yunsong Li (2007)
10.1007/978-1-4939-2205-5
Insoluble Proteins
E. Garcia-Fruitós (2015)
10.1039/b907656e
Structure-energy relations in hen egg white lysozyme observed during refolding from a quenched unfolded state.
T. Y. Cho (2009)
10.1002/JPS.20890
Effect of hydration on the secondary structure of lyophilized proteins as measured by fourier transform infrared (FTIR) spectroscopy.
S. Luthra (2007)
10.1002/jps.22753
Structure, stability, and mobility of a lyophilized IgG1 monoclonal antibody as determined using second-derivative infrared spectroscopy.
B. Murphy (2012)
10.1016/J.IJPHARM.2005.08.006
Effect of lyophilization on the structure and phase changes of PEGylated-bovine serum albumin.
Virgílio Tattini (2005)
10.1016/J.EJPB.2006.08.014
Conformational analysis of protein secondary structure during spray-drying of antibody/mannitol formulations.
S. Schuele (2007)
10.1007/978-0-387-36063-8_5
Application of Spectroscopic and Calorimetric Techniques in Protein Formulation Development
A. Wilcox (2006)
10.1080/10408390500511896
Baby Foods: Formulations and Interactions (A Review)
A. Nasirpour (2006)
10.1007/s00726-007-0506-3
Biotechnology applications of amino acids in protein purification and formulations
T. Arakawa (2007)
10.3390/molecules191220888
Combined Dynamic Light Scattering and Raman Spectroscopy Approach for Characterizing the Aggregation of Therapeutic Proteins
E. Lewis (2014)
10.1002/JPS.10562
Effects of potassium bromide disk formation on the infrared spectra of dried model proteins.
J. D. Meyer (2004)
10.1002/JPS.21190
Polysorbates 20 and 80 used in the formulation of protein biotherapeutics: structure and degradation pathways.
B. Kerwin (2008)
10.1016/J.BEJ.2007.01.014
Organic solvents effect on the secondary structure of araujiain hI, in different media
E. Quiroga (2007)
10.1007/s00726-011-1151-4
Relationship between digestibility and secondary structure of raw and thermally treated legume proteins: a Fourier transform infrared (FT-IR) spectroscopic study
M. Carbonaro (2011)
esiccation tolerance : From genomics to the field
livier Leprince (2010)
10.1211/0022357021778448
Recent trends in stabilizing protein structure upon encapsulation and release from bioerodible polymers
C. Pérez (2002)
10.1006/ABIO.2001.5337
Fourier transform infrared spectrometric analysis of protein conformation: effect of sampling method and stress factors.
M. van de Weert (2001)
10.1002/jps.23133
Comparability of protein therapeutics: quantitative comparison of second-derivative amide I infrared spectra.
Jennifer D'antonio (2012)
10.1007/s11095-008-9575-6
Preparation of Active Proteins, Vaccines and Pharmaceuticals as Fine Powders using Supercritical or Near-Critical Fluids
S. Cape (2008)
10.1002/JPS.1098
The effects of Tween 20 and sucrose on the stability of anti-L-selectin during lyophilization and reconstitution.
L. Jones (2001)
FTIR STUDY ON THE INTERACTION OF QUERCETIN AND AMANTADINE WITH EGG ALBUMIN
S. Bakkialakshmi (2013)
10.1007/978-1-4615-0557-0
Rational Design of Stable Protein Formulations
J. F. Carpenter (2002)
10.1016/J.IJADHADH.2015.06.004
Rheological behavior and bonding performance of an alkaline soy protein suspension
Alejandro Bacigalupe (2015)
10.1002/9781118354698.CH12
Biophysical Analyses Suitable for Chemistry, Manufacturing, and Control Sections of the Biologic License Application (BLA)
Z. Shahrokh (2014)
10.1002/JPS.1032
Dry powders of stable protein formulations from aqueous solutions prepared using supercritical CO(2)-assisted aerosolization.
S. Sellers (2001)
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