Effects of surfactant systems on metformin transport
Abstract
This work has focused on the investigations of carrier and absorption enhancing systems for the hydrophilic drug metformin when delivered orally. The influence of both water-in-oil (W/O) and oil-in-water (O/W) emulsions containing metformin in the aqueous phase on oral metformin bioavailability was studied in the rat. A water-in-isopropyl myristate emulsion stabilised with sorbitan monooleate (Span 80) and bovine serum albumin (BSA), an OAV emulsion stabilised with cholesteryl poly (24) oxyethylene ether (Solulan C24) and Span 80 prepared with soybean oil and an OAV emulsion stabilised with sorbitan monostearate (Span 60) with sesame oil as the continuous phase were formulated, characterised and tested in vivo. The oral administration of emulsions modifies the absorption of metformin in rat. Histological investigations provided some clues as to the cause of increase in metformin absorption. Most likely are changes to the intestinal membrane and, in some cases to the junctional complexes caused by the surface active compounds and fatty acids present in the formulations. Knowledge of the reversibility of these effects was crucial. Allowing the intestinal cells to recover after dosing for three days, suggests that all changes that were detected were, indeed, reversible. The effects of the non-ionic surfactants polysorbate 20, 60, 85, Solulan C24 and a lanolin-based poly(16)oxyethylene ether (Solulan 16) on epithelial integrity of the Caco-2 cells monolayers were studied. The…
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