The Role of Molecular Mobility in Governing the Physical Stability of Amorphous Pharmaceuticals

Abstract

The amorphous state is probably one of the most interesting and curious state of matter. This confirms large number of futuristic and next-generation materials that turned out to be partially or completely amorphous. However, physical properties of amorphous solids are incomprehensible in many aspects. Even the glassy formation is considered as one of the most important unsolved problems of solid state physics. Understanding what drives supercooled liquids and glasses towards crystallization is fundamental not only in the context of unexplained issues of condensed matter physics, but also many practical applications. In this Ph. D. dissertation I have made an attempt to answer the most important in recent days questions that relate to molecular dynamics of amorphous materials. The robustness of the ‘universal’ relationships between dynamics and crystallization tendencies of glass-formers was also uncovered. The first raised issue concerned dynamical properties of amorphous materials depending on the preparation method. Collected results for compounds of great pharmaceutical interest, Telmisartan and antibiotics, remarkably showed that dynamical properties of amorphous substances prepared using two different amorphization routes (vitrification and cryomilling) might differ. However, observed discrepancies in molecular dynamics results only from the fact that during manufacturing they uptake different amount of water from the surroundings, and this absorbed water has critical influence on their dynamical properties. Particularly interesting here are results for antibiotics. The presence of y-relaxation, of most probably the same molecular origin, was reported in anhydrous glassy state of Clarithromycin and Roxithromycin. In the anhydrous vitrified Azithromycin the lack of y-relaxation was reported, while in cryomilled amorphous sample this process became suddenly activated due to the presence of water.