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Investigation of freezing- and thawing-induced biological, chemical, and physical changes to enoxaparin solution
Citation
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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The definitive published version is available online at: http://interscience.wiley.com
Official URL: http://interscience.wiley.com
Abstract
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 -196°C. 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 -196°C 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 |
| Downloads: | 3 View Download Statistics |
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