EFFECT OF VARIOUS LIPID BILE-SALT MIXED MICELLES ON THE INTESTINAL-ABSORPTION OF AMPHOTERICIN-B IN RAT

Amphotericin-B (AmB), a lipophilic polyene antibiotic, is the drug of choice in the treatment of many serious mycotic diseases. The solubili ty and gastrointestinal membrane permeability (P-app) of AmB in mixed micellar systems were examined. Membrane permeability was determined u sing a rat gut perfusion method. The mixed micellar systems studied co ntained the bile salt in association with fatty acid. All mixed micell ar systems enhanced the absorption of AmB relative to the simple micel le. These results have shown that mixed micelles can enhance the absor ption of AmB to a greater extent relative to nonmicellar and simple mi cellar systems. Maximum enhancement (>20-fold) in the rate of AmB abso rption was obtained with the sodium desoxycholate/soya lecithin 40:40 mM system. These results offer a possible explanation for the reported enhancement in gastrointestinal absorption of AmB when coadministered with lipid-bile salt mixed micelles, and these systems can be used as a vehicle for designing novel drug delivery systems for poorly absorb able drug(s).