Mechanism of the intestinal absorption of drugs from oil in water emulsions. IV. Absorption from emulsions containing the higher concentration of emulsifier.

Abstract

Mechanism of the absorption of drugs from oil in water emulsions to which emulsifier was added at higher concentration was studied in rat large intestine, using in situ recirculation technique. Synthesized esters of fatty acids, tri-n-butyrin and ethyl laurate as oil and polysorbate-80 as emulsifier were chosen. Two model drugs, vitamin A acetate (VAA) and phenylbutazone (PB) were chosen for absorption studies. VAA was distributed into oily, and micellar phases, not into aqueous phase. Oil/micelle partition coefficient of VAA was determined using ultrafiltration method. PB was distributed into oily and micellar phases, and a few into aqueous phase in spite of its nearly complete ionization at neutral pH. In the absorption of VAA, amount of the drug in micellar phase was a critical factor for absorption as VAA was absorbed mainly via micellar phase. VAA was released from micelles adsorbed on mucosal layer and was absorbed, and this process was interfered with oil droplets adsorbed on mucosal layer. In the absorption of PB, amount of the drug in aqueous phase was a critical factor for the absorption as PB was absorbed mainly via aqueous phase. Absorption process of PB was not interfered with oil droplets adsorbed on mucosal layer.