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The in vivo elimination and tissue distribution (2 h after administration) of various types of formulations of alpha-tocopherol as a model drug were examined in rats. An organic cosolvents formulation of alpha-tocopherol (alpha-tocopherol/EtOH/polyethylene glycol 400) was rapidly removed from the blood circulation, the ratio of the distributed alpha-tocopherol was 20% in the lungs, about 70% in the liver and about 10% in the spleen. The main reason for this was considered to be the appearance of droplets more than 10 microns in diameter in the blood. Elimination of the micelle formulation using Brij58 from the blood was the most rapid, followed by Tween80 and HCO60. This order is thought to be due to the difference in the polyoxyethylene group among these surfactants. In liposome formulations, liposomes having a diameter of about 80 nm were the most stable in the blood circulation, and alpha-tocopherol was distributed in the reticuloendothelial system (RES) in the smallest ratio. The uptake of liposomes by the spleen and lungs depended on the liposome size. The uptake by the liver was in the decreasing order of 28 nm &gt;&gt; 42 nm, 151 nm, 195 nm, 3656 nm &gt; 106 nm &gt; 75 nm. The 100 nm lipid emulsion was eliminated from the blood more rapidly than the 100 nm liposome formulation.

Blood Clearance and Tissue Distribution of Various Formulations of .ALPHA.-Tocopherol Injection after Intravenous Administration.