Document Detail

Partially crystalline systems in lyophilization: I. Use of ternary state diagrams to determine extent of crystallization of bulking agent.
MedLine Citation:
PMID:  15729706     Owner:  NLM     Status:  MEDLINE    
Two model ternary systems: water-glycine-raffinose and water-glycine-trehalose were investigated to determine the extent of glycine crystallization in frozen solutions. The use of such partially crystalline systems allows primary drying to be carried out substantially above the collapse temperature. Differential scanning calorimetry (DSC) and variable temperature X-ray diffractometry (XRD) were used to monitor phase transitions in frozen systems as well as to determine the T'g. Aqueous solutions containing different glycine to carbohydrate weight ratios were first cooled to -60 degrees C and then warmed to room temperature. In both raffinose and trehalose systems, when the initial glycine to sugar (raffinose pentahydrate or trehalose dihydrate) ratio was <1, glycine crystallization was not detected. When the ratio was >or=1, partial glycine crystallization was observed during warming. The presence of amorphous glycine caused the T'g to be substantially lower than that of the solution containing only the carbohydrate. To determine the extent of glycine crystallization, the solutions were annealed for 5 h just above the temperature of glycine crystallization. The T'g observed in the second warming curve was very close to that of the carbohydrate solution alone, indicating almost complete glycine crystallization. These studies enabled the construction of the water-rich sections of the raffinose-glycine-water and trehalose-glycine-water state diagrams. These diagrams consist of a kinetically stable freeze-concentrated solution and a doubly unstable glassy region, which readily crystallizes during cooling or subsequent warming. In addition, there is an intermediate region, where during the experimental timescale, there appears to be hindered glycine nucleation but unhindered crystal growth. To obtain substantially crystalline glycine in the frozen solutions, the glycine to carbohydrate ratios should be >or=1.
Koustuv Chatterjee; Evgenyi Y Shalaev; Raj Suryanarayanan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  94     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-03     Completed Date:  2005-08-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  798-808     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2005 Wiley-Liss, Inc.
College of Pharmacy, 308, Harvard St. S.E., University of Minnesota, Minneapolis, Minnesota 55455, USA.
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MeSH Terms
Calorimetry, Differential Scanning
Chemistry, Physical
Crystallography, X-Ray
Excipients / chemistry*
Freeze Drying*
Glycine / chemistry
Physicochemical Phenomena
Raffinose / chemistry
Trehalose / chemistry
Reg. No./Substance:
0/Excipients; 0/Solutions; 512-69-6/Raffinose; 56-40-6/Glycine; 99-20-7/Trehalose

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

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