O W LIPID EMULSIONS FOR PARENTERAL DRUG-DELIVERY .2. EFFECT OF COMPOSITION ON PHARMACOKINETICS OF INCORPORATED DRUG/

The potential usefulness of O/W lipid emulsions as injectable drug del ivery systems for lipophilic drugs was examined using a model lipophil ic drug, sudan II (clogP=5.4) in the normal rats. The standard lipid e mulsion composed of soybean oil and egg yolk phosphatides increased th e blood concentration of sudan II after i.v. injection when compared w ith its solubilized solution by plasma. However, it was still lower th an that of the oil particles, and the distribution of sudan II to live r, lungs, adipose tissue, heart, and muscle was not altered, and only that to brain and kidneys was decreased. Herein, the effect of extensi ve alterations in the lipid emulsion composition on the blood concentr ation and organ distribution of sudan II was examined in comparison wi th the standard formulation. Addition of cholesterol, use of pure egg yolk phosphatidylcholine, use of phospholipids with saturated alkyl ch ain, use of saturated long chain triglycerides, and use of saturated m edium chain triglycerides were tested. The oil particles of all tested lipid emulsions were still located in plasma space, and use of satura ted medium chain triglycerides was the most effective way to increase blood concentration of sudan II, resulting in higher distribution to l iver, lungs, spleen, and brain. This was caused by the increase of the steady-state partition of sudan II to the oil particles, and not by a lteration of their organ distribution clearance.