Document Detail


Diacyl glyceryl ester prodrugs for slow release in the skin: synthesis and in vitro degradation and absorption studies for naproxen derivatives.
MedLine Citation:
PMID:  10603609     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diacyl glyceryl ester derivatives of naproxen were synthesized and tested for transdermal and dermal administration. Diacyl derivatives of aliphatic acids of various chain length were compared. The pharmaceutical properties of these compounds, such as lipophilicity, hydrolysis in a buffer solution at various pH values and degradation in human serum and hairless mouse skin homogenate, were investigated. All the diacyl derivatives were relatively stable in a neutral buffer solution, but were rapidly degraded to release naproxen in human serum and hairless mouse skin homogenate. The diacyl compounds could not penetrate hairless mouse skin in vitro. However, significant absorption into the skin could be measured, and this increased with increasing lipophilicity. A more than 100-fold difference in absorption was observed. The prodrugs were slowly hydrolyzed to naproxen inside the skin. The release of naproxen to the receptor compartment of diffusion cells showed that this type of prodrug could be used for controlled drug delivery.
Authors:
T Thorsteinsson; M Másson; T Loftsson; G G Haraldsson; E Stefánsson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Die Pharmazie     Volume:  54     ISSN:  0031-7144     ISO Abbreviation:  Pharmazie     Publication Date:  1999 Nov 
Date Detail:
Created Date:  2000-01-31     Completed Date:  2000-01-31     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  9800766     Medline TA:  Pharmazie     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  831-6     Citation Subset:  IM    
Affiliation:
Department of Pharmacy, University of Iceland, Reykjavik, Iceland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis,  chemistry,  pharmacokinetics*
Buffers
Chromatography, High Pressure Liquid
Chromatography, Thin Layer
Delayed-Action Preparations
Diglycerides / chemical synthesis,  chemistry,  pharmacokinetics*
Female
Half-Life
Humans
Hydrogen-Ion Concentration
Mice
Mice, Hairless
Mice, Inbred C3H
Naproxen / chemical synthesis,  chemistry,  pharmacokinetics*
Prodrugs / chemical synthesis,  chemistry,  pharmacokinetics*
Skin / metabolism
Skin Absorption*
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Buffers; 0/Delayed-Action Preparations; 0/Diglycerides; 0/Prodrugs; 22204-53-1/Naproxen

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


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