Abstract | PURPOSE: The objective of this study was to synthesize anhydride prodrugs for prolong action to shield the carboxylic acid group from irritative effects and to temporary hydrophobize the drug so that it becomes accessible to aqueous media when the anhydride residue is hydrolyzed. METHODS: RESULTS:
Ibuprofen was bound to aliphatic and aromatic acids via an anhydride bond in high reaction yields (>85%) with high mixed anhydride content (>80%). The mix anhydride was purified by chromatography and stored at 4 degrees C to minimize conversion into the symmetric anhydride. These anhydride derivatives hydrolyzed at different time intervals depending on the hydrophobicity of conjugated acid. In vivo testing of the ibuprofen anhydride derivatives for analgesic effect indicated an extended action of the drug for over 24 h as a function of the fatty acid chain length. CONCLUSION:
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Authors | Osnat Shaaya, Amir Magora, Tzviel Sheskin, Neeraj Kumar, Abraham J Domb |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 20
Issue 2
Pg. 205-11
(Feb 2003)
ISSN: 0724-8741 [Print] United States |
PMID | 12636158
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Anhydrides
- Anti-Inflammatory Agents, Non-Steroidal
- Prodrugs
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Topics |
- Anhydrides
(analysis, chemistry, pharmacokinetics)
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(analysis, chemistry, pharmacokinetics, therapeutic use)
- Edema
(drug therapy)
- Female
- Prodrugs
(analysis, chemistry, pharmacokinetics)
- Rats
- Rats, Sprague-Dawley
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