Water-in-oil microemulsions containing medium-chain fatty acids/salts: formulation and intestinal absorption enhancement evaluation

Constantinides, P.P.; Welzel, G.; Ellens, H.; Smith, P.L.; Sturgis, S.; Yiv, S.H.; Owen, A.B.

Pharmaceutical Research 13(2): 210-215


ISSN/ISBN: 0724-8741
PMID: 8932438
DOI: 10.1023/a:1016030812272
Accession: 034227852

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Purpose: Water-in-oil (w/o) microemulsions have been developed which, in addition to non-ionic medium-chain glycerides, incorporate ionic lipids, primarily medium-chain fatty acids, such as capryiic (C-8) capric (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 water-soluble and poorly absorbed marker molecule. Methods: Phase diagrams were constructed where C-8/C-10 or C-12 fatty acids were treated as lipophilic surfactants and their sodium salts as hydrophilic ones. The anesthetised rat model was employed to evaluate Calcein absorption upon a single intraduodenal administration from a solution and the various w/o microemulsions. Results: A wide range of clear and transparent w/o microemulsions were obtained at ambient temperature either in liquid 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 intraduodenal 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 effective in improving bioavailability. The absorption enhancement activity of the fatty acids/salts followed the order C-8 apprxeq C-10 gt 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 glycerides and fatty acids/salts in microemulsion formulations to improve intestinal absorption of water-soluble compounds.