Abstract
Amphotericin-B (AmB), a lipophilic polyene antibiotic, is the drug of choice in the treatment of many serious mycotic diseases. The solubility and gastrointestinal membrane permeability (Papp) of AmB in mixed micellar systems were examined. Membrane permeability was determined using a rat gut perfusion method. The mixed micellar systems studied contained the bile salt in association with fatty acid. All mixed micellar systems enhanced the absorption of AmB relative to the simple micelle. These results have shown that mixed micelles can enhance the absorption of AmB to a greater extent relative to nonmicellar and simple micellar systems. Maximum enhancement (>20-fold) in the rate of AmB absorption 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 absorbable drug(s).
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