Metody poprawy fizycznej stabilności amorficznej formy ezetimibu

Abstract

This dissertation is concerned with the physical stability of the amorphous form of the drug, ezetimibe. Experiments performed by means of Differential Scanning Calorimetry (DSC), Broadband Dielectric Spectroscopy (BDS) as well as X-Ray Diffraction (XRD) show that the disordered form of ezetimib stored at room temperature starts reverting to its crystalline form just after two weeks of amorphization. This of course also results in a loss of its superior properties e.g. higher water solubility as well as better bioavailability. In order to inhibit the ezetimib’s re-crystallization three different methods have been applied. The drug was mixed with a polymer named Soluplus, with a small molecular weight excipient – indapamid drug, as well as it being incorporated inside the nonometric scale pores present in silica materials: Aeroperl 300 and Neusilin US2. Results based on a series of experiments show us that besides Aeroperl 300, all used methods can effectively stabilize the amorphous form of the ezetimibe drug.