Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2486305 | Journal of Pharmaceutical Sciences | 2006 | 8 Pages |
Abstract
PROLI/NO is an agent of structure XN(O)âNONa (X = L-prolyl) whose 2-s half-life for nitric oxide (NO) release at physiological pH makes it an excellent prodrug for localizing NO's therapeutic effects at the site of application, but a difficult one to formulate and certify as pure. Despite its extraordinary thermal and hydrolytic instability, however, PROLI/NO could be formulated as an injectable drug by dissolving it in cold 0.1 M sodium hydroxide containing 5% D-mannitol, then quickly ultrafiltering and lyophilizing it in evacuated septum vials. No evidence for decomposition was seen in the contents of these evacuated vials when stored at â20°C over a 140-day observation period, as judged by quantifying NO release in simulated infusate solutions (10 mM carbonate/bicarbonate, pH 10.5). The only hydrolysis products detected were NO, nitrite ion, proline, and N-nitrosoproline, all products of normal human physiological processes. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association
Keywords
Related Topics
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Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
David J. Waterhouse, Joseph E. Saavedra, Keith M. Davies, Michael L. Citro, Xia Xu, Douglas A. Powell, George J. Grimes, Gopal K. Potti, Larry K. Keefer,