O/W Lipid Emulsions for Parenteral Drug Delivery. II. Effect of Composition on Pharmacokinetics of Incorporated Drug

Abstract

The potential usefulness of O/W lipid emulsions as injectable drug delivery systems for lipophilic drugs was examined using a model lipophilic drug, sudan II (clogP = 5.4) in the normal rats. The standard lipid emulsion composed of soybean oil and egg yolk phosphatides increased the blood concentration of sudan II after i.v. injection when compared with its solubilized solution by plasma. However, it was still lower than that of the oil particles, and the distribution of sudan II to liver, lungs, adipose tissue, heart, and muscle was not altered, and only that to brain and kidneys was decreased. Herein, the effect of extensive alterations in the lipid emulsion composition on the blood concentration and organ distribution of sudan II was examined in comparison with the standard formulation. Addition of cholesterol, use of pure egg yolk phosphatidylcholine, use of phospholipids with saturated alkyl chain, use of saturated long chain triglycerides, and use of saturated medium chain triglycerides were tested. The oil particles of all tested lipid emulsions were still located in plasma space, and use of saturated medium chain triglycerides was the most effective way to increase blood concentration of sudan II, resulting in higher distribution to liver, 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 alteration of their organ distribution clearance.