Document Detail


Freeze-drying of proteins in glass solids formed by basic amino acids and dicarboxylic acids.
MedLine Citation:
PMID:  19122314     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The purpose of this study was to produce and characterize glass-state amorphous solids containing amino acids and organic acids that protect co-lyophilized proteins. Thermal analysis of frozen solutions containing a basic amino acid (e.g., L-arginine, L-lysine, L-histidine) and a hydroxy di- or tricarboxylic acid (e.g., citric acid, L-tartaric acid, DL-malic acid) showed glass transition of maximally freeze-concentrated solute at temperatures (T'g) significantly higher than those of the individual solute solutions. Mixing of the amino acid with some dicarboxylic acids (e.g., oxalic acid) also suggested an upward shift of the transition temperature. Contrarily, combinations of the amino acid with monocarboxylic acids (e.g., acetic acid) had T'gs between those of the individual solute solutions. Co-lyophilization of the basic amino acids and citric acid or L-tartaric acid resulted in amorphous solids that have glass transition temperatures (Tg) higher than the individual components. Mid- and near-infrared analysis indicated altered environment around the functional groups of the consisting molecules. Some of the glass-state excipient combinations protected an enzyme (lactate dehydrogenase, LDH) from inactivation during freeze-drying. The glass-state excipient combinations formed by hydrogen-bonding and electrostatic interaction network would be potent alternative to stabilize therapeutic proteins in freeze-dried formulations.
Authors:
Ken-ichi Izutsu; Saori Kadoya; Chikako Yomota; Toru Kawanishi; Etsuo Yonemochi; Katsuhide Terada
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chemical & pharmaceutical bulletin     Volume:  57     ISSN:  0009-2363     ISO Abbreviation:  Chem. Pharm. Bull.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-05     Completed Date:  2009-04-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0377775     Medline TA:  Chem Pharm Bull (Tokyo)     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  43-8     Citation Subset:  IM    
Affiliation:
National Institute of Health Sciences, Setagaya, Tokyo, Japan. Izutsu@nihs.go.jp
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MeSH Terms
Descriptor/Qualifier:
Amino Acids, Basic / chemistry*
Dicarboxylic Acids / chemistry*
Freeze Drying
Glass*
L-Lactate Dehydrogenase / chemistry
Proteins / chemistry*
Chemical
Reg. No./Substance:
0/Amino Acids, Basic; 0/Dicarboxylic Acids; 0/Proteins; EC 1.1.1.27/L-Lactate Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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