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Investigation of freezing- and thawing-induced biological, chemical, and physical changes to enoxaparin solution


Patel, R and Narkowicz, CK and Jacobson, GA, Investigation of freezing- and thawing-induced biological, chemical, and physical changes to enoxaparin solution, Journal of Pharmaceutical Science, 98, (3) pp. 1118 - 1128. ISSN 0022-3549 (2009) [Refereed Article]

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DOI: doi:10.1002/jps.21483


This study investigated the effect of freezing and thawing on the biological, physical, and chemical properties of enoxaparin solution. Solutions were frozen and thawed under different conditions, in the presence or absence of dimethyl sulfoxide (DMSO) or 1,2-propanediol (1,2-PD), and the antifactor Xa (AFXa) activity was determined. Enoxaparin solution lost more than 60% of its AFXa activity when thawed rapidly after freezing at -196C. The loss of AFXa activity was less with higher freezing temperatures and increased with the number of freeze/thaw cycles, but was independent of the duration of freezing. Slow freezing to -196C with rapid thawing, or rapid freezing with slow thawing, resulted in negligible loss of AFXa activity. The loss of AFXa activity did not involve the loss of N-sulfate groups, the breakdown of glycosidic bonds or the glassy state transition. Controlling the freezing or thawing conditions, dilution with water or addition of a small percentage of DMSO ameliorated the loss of enoxaparin AFXa activity. The loss in AFXa activity was found by size exclusion chromatography to be primarily due to aggregation and was reversed by sonication in the presence of DMSO. These results may provide insight into solutions for the long-term storage of concentrated or diluted enoxaparin.

Item Details

Item Type:Refereed Article
Keywords:AFXa activity enoxaparin freezing thawing aggregation low molecular weight heparin
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Pharmaceutical sciences
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Public health (excl. specific population health) not elsewhere classified
UTAS Author:Patel, R (Dr Rahul Patel)
UTAS Author:Narkowicz, CK (Dr Christian Narkowicz)
UTAS Author:Jacobson, GA (Professor Glenn Jacobson)
ID Code:53239
Year Published:2009
Web of Science® Times Cited:12
Deposited By:Pharmacy
Deposited On:2008-11-14
Last Modified:2010-06-29
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