Eflucimibe

Abstract: Eflucimibe is a drug, which displays hypocholesterolemic and anti-atherosclerotic properties in animal models. The solubility of eflucimibe in supercritical carbon dioxide has been investigated with an apparatus based on an analytical open circuit method. Solubility values have been measured at 308.15 and 318.15 K in the pressure range 8–30 MPa. Solubility appears to be an increasing function of both temperature and pressure. The two co-solvents investigated, ethanol and dimethylsulphoxide, are found to significantly enhance the solubility. Solubility data are reported for the 308.15 K isotherm at different total pressures and different solvent/co-solvent ratios. The observed co-solvent effects can be explained not only by density effects, but by the effect of molecular interactions on the basis of compound solubility parameters.

Abstract: Nucleation and metastability of the eflucimibe (S)-2',3',5'-trimethyl-4'-hydroxy-dodecylthiophenyl-acetanilide, a new acyl-coenzyme A:cholesterol O-acyltransferase (ACAT) inhibitor, have been investigated according to a polythermal method. Eflucimibe exhibits two polymorphs, A and B, which crystallize simultaneously (concomitant polymorphs). The focus of this study was on the effect of the cooling rate, the initial concentration, and the seeds on metastability and polymorphism of eflucimibe. For nonseeded crystallization, it was found that the metastable zone width is large (primary nucleation) and fulfills well the linear relation between log ΔT max and log(dT/dt). In addition, the X-ray powder diffraction and differential scanning calorimetry analyses of the powder obtained show that the desired polymorph (pure A form) is difficult to obtain. On the contrary, for seeded experiments, the metastable zone width is significantly reduced (secondary nucleation) and the occurrence of polymorphism is controlled by seeding with the desired polymorph.

Abstract: Lipid-lowering strategies, particularly with statins, have been extremely useful in the prevention of cardiovascular disease. However, many patients who receive statin monotherapy do not achieve the desired cardiovascular benefits. Accumulation of cholesteryl esters within macrophages constitutes the hallmark of foam cells during atherogenesis. The action of acyl-coenzyme A (CoA): cholesterol acyltransferase (ACAT) leads to formation of cholesterol esters. There are two different ACAT isoforms: ACAT1 and ACAT2. A considerable interest to develop ACAT inhibitors has been emerging. This review has been focused on the current knowledge about a new ACAT inhibitor, F12511 or eflucimibe, and more particularly on its antiatherosclerotic properties.