TITLE

Mechanistic Understanding of Oral Drug Absorption Enhancement of Cromolyn Sodium by an Amino Acid Derivative

AUTHOR(S)
Adam Alani; Joseph Robinson
PUB. DATE
January 2008
SOURCE
Pharmaceutical Research;Jan2008, Vol. 25 Issue 1, p48
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Abstract Purpose  Examine the oral absorption enhancement mechanism of cromolyn sodium by sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) by evaluating the effect of SNAC on cromolyn sodium lipophilicity and changes in Caco-2 cell membrane fluidity. Materials and Methods  Standard Shake-flask method was used to evaluate the effect of SNAC on the lipophilicity of cromolyn sodium. The measurements were carried out in three partitioning solvents with varying hydrogen-bonding properties. Steady state fluorescence emission anisotropy technique was used to evaluate the effect of SNAC with/without cromolyn sodium on Caco-2 cell membrane fluidity. Results  The lipophilicity measurements showed that SNAC had no influence on the lipophilicity of cromolyn sodium in the three partitioning solvent systems. The findings of the steady-state fluorescence anisotropy showed that SNAC increases the membrane fluidity of the Caco-2 cells in a concentration dependent manner. The increase in fluidity with SNAC was seen in the presence and absence of cromolyn sodium and the presence of cromolyn sodium did not augment the effect of SNAC on membrane fluidity. Conclusions  The increase in membrane fluidity by SNAC plays a pivotal role in the permeation enhancement mechanism of cromolyn sodium. Therefore, the increase in permeation is a result of changing Caco-2 cell membrane fluidity resulting in change in membrane integrity and not due to an increase in the lipophilicity of cromolyn sodium through its interaction with SNAC.
ACCESSION #
28383682

 

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