X-ray amorphous and disordered crystalline pharmaceutical materials: A characterization scheme using X-ray powder diffraction

ANYL 203

Simon Bates, SBATES@SSCI-INC.com, SSCI Inc, 3065 Kent Ave, West Lafayette, IN 47906
Amorphous and disordered pharmaceutical materials pose a significant challenge to the development of acceptable products. In general, they may have some attractive properties like increased solubility, but these properties are highly dependent on processing, and in addition physical and chemical stability is usually a concern. X-ray powder diffraction (XRPD) measurements taken during cryo-grinding experiments performed on pharmaceutical API material have revealed two very different disordering processes. The first is a discreet thermodynamic disordering process that occurs when a crystalline material looses symmetry operators (translation, orientation, conformation) to become a mesophase or thermodynamic amorphous material. The second is a more continuous kinetic process rendering long range order crystalline material into defected crystalline material eventually producing short range order and a kinetic glassy state. Under continued disordering, the kinetic glassy material may transform into the thermodynamic amorphous state. Examples will be presented from cryo-grinding and dehydration studies that demonstrate modeling of XRPD data, pair wise distribution functions (PDF) and a new disordered material characterization scheme.