Phospholipid micoremulsions have been suggested as a drug-delivery system for hydrophobic compounds. In this study hydrophobicity was achieved by derivatizing with cholesterol. Cholesteryl ibuprofen (3) and cholesteryl flufenamate (4) were synthesized. 3 was isolated as an amorphous, white solid with a melting range of 114-120 degrees C. 4 was isolated as a crystalline, white solid with a melting range of 145-148 degrees C. The proposed structures of 3 and 4 were supported by IR, NMR, MS, and organic microanalysis. Phospholipid:cholesteryl ester microemulsions were prepared by the addition of a 1-propanol solution of the cholesteryl ester, other lipids, and phospholipid to a rapidly mixing KCl/KBr solution. The hydrophobic phase was modified by the addition of cholesteryl oleate or triolein to study the effect of the fluidity of the hydrophobic core on the formation of the microemulsions. The results indicated that a molar ratio of 75:25 and a total lipid concentration of 60 mg/mL consistently gave microemulsions with a mean size of 100-150 nm. In addition, the formation of eutectic mixtures of 3 and 4 with cholesteryl oleate were determined to be 16% (w/w) for 3 and 12% (w/w) for 4; melting points were 35.2 and 45.2 degrees C, respectively. The solubilities of 3 and 4 in triolein were determined to be 13.2% (w/w) and 11.5% (w/w), respectively. Other investigators have shown that if the core of a phospholipid:cholesteryl estermicroemulsion exists in a liquid state at physiologic temperature, the turnover of the cholesteryl esters from these microemulsions occurs at a faster rate.(ABSTRACT TRUNCATED AT 250 WORDS)