Physical Stability and Viscoelastic Properties of Co-Amorphous Ezetimibe/Simvastatin System

The purpose of this paper is to examine the physical stability as well as viscoelastic properties of the binary amorphous ezetimibe⁻simvastatin system. According to our knowledge, this is the first time that such an amorphous composition is prepared and investigated. The tendency toward re-crystallization of the amorphous ezetimibe⁻simvastatin system, at both standard storage and elevated temperature conditions, have been studied by means of X-ray diffraction (XRD). Our investigations have revealed that simvastatin remarkably improves the physical stability of ezetimibe, despite the fact that it works as a plasticizer. Pure amorphous ezetimibe, when stored at room temperature, begins to re-crystallize after 14 days after amorphization. On the other hand, the ezetimibe-simvastatin binary mixture (at the same storage conditions) is physically stable for at least 1 year. However, the devitrification of the binary amorphous composition was observed at elevated temperature conditions (T = 373 K). Therefore, we used a third compound to hinder the re-crystallization. Finally, both the physical stability as well as viscoelastic properties of the ternary systems containing different concentrations of the latter component have been thoroughly investigated.