O W LIPID EMULSIONS FOR PARENTERAL DRUG-DELIVERY .1. PHARMACOKINETICSOF THE OIL PARTICLES AND INCORPORATED SUDAN-II/

The potential usefulness of oil in water (O/W) lipid emulsions as pare nteral drug delivery system for lipophilic drugs was examined in tumor -bearing rats. A model lipophilic drug, sudan II (PCoct=226000), was f ormulated in five lipid emulsions consisting of soybean oil and variou s surfactants. Compared with HCO-60 micellar and plasma solutions of s udan II, the blood concentration of sudan II was markedly elevated by administration as a lipid emulsion. However, the distribution of sudan II to the liver, lungs, spleen, and adipose tissue was not altered, a nd that to the brain, heart, kidneys, muscle, and tumor was slightly d ecreased. To understand these results, pharmacokinetic analysis was pe rformed using a newly derived compartmental model, and moreover, the o rgan distribution clearance was analyzed. It was suggested that the oi l particles deliver the incorporated drug selectively to the liver, lu ngs, and spleen, and the speed of delivery could be surpressed by usin g HCO-60. However, in the case of sudan II, its rapid release from the oil particles after i.v. injection prevented a drastic alteration in the distribution of sudan II. The simulation studies suggested that a considerable decrease in the release rate or an increase in partition coefficient (experimentally more than 10(8)) would be required for del ivery.