Purpose. Water-in-oil (w/o) microemulsions have been developed which,
in addition to non-ionic medium-chain glycerides, incorporate ionic li
pids, primarily medium-chain fatty acids, such as caprylic (C-8) capri
c (C-10) and lauric (C-12) acids and their corresponding sodium salts.
The absorption enhancing activity of w/o microemulsions incorporating
these lipids was evaluated in the rat using Calcein (MW = 623) a wate
r-soluble and poorly absorbed marker molecule. Methods. Phase diagrams
were constructed where C-8/C-10 Or C-12 fatty acids were treated as l
ipophilic surfactants and their sodium salts as hydrophilic ones. The
anesthetised rat model was employed to evaluate Calcein absorption upo
n a single intraduodenal administration from a solution and the variou
s w/o microemulsions. Results. A wide range of clear and transparent w
/o microemulsions were obtained at ambient temperature either in liqui
d or solid form when a fixed blend of medium chain fatty acid/salt was
titrated by a fixed ratio of the oil containing the oil-soluble mono-
and diglycerides and deionized water or physiological saline. Upon in
traduodenal administration in the anesthetised rat, the absorption of
Calcein was improved from about 2% in aqueous solution up to about 37%
in w/o microemulsions. Solid and liquid formulations were equally eff
ective in improving bioavailability. The absorption enhancement activi
ty of the fatty acids/salts followed the order C-8 approximate to C-10
> C-12 Absorption enhancement of Calcein was significantly reduced in
the absence or presence of low levels of C-8/C-10 mono-/diglycerides.
Conclusions. These results further support the use of medium-chain gl
ycerides and fatty acids/salts in microemulsion formulations to improv
e intestinal absorption of water-soluble compounds.