Characteristic evaluation of the pseudo-polymorphism of amorphous atorvastatin calcium hydrates by terahertz spectroscopy

Abstract

In order to scientifically elucidate the difference in the dissolution characteristics of crystalline atorvastatin calcium (ATCH) and the amorphous ATC solids (ATC30 and ATC120) obtained by the grinding for 30 and 120 min, X-ray powder diffractometry (XRD), infrared (IR) spectroscopy, near-infrared (NIR) spectroscopy, terahertz (THz) spectroscopy and thermal analysis were measured, and compared with the result of dissolution kinetics analysis. ATCH showed characteristic crystalline XRD pattern, but ATC30 and ATC120 showed no XRD peak profiles, meaning that those completely transformed into the amorphous solids. ATCH, ATC30 and ATC120 showed also individual characteristic IR and NIR spectra, respectively. ATCH contained 3 mol of crystal water, but ATC30 and ATC120 contained weakly binding adsorbed water in the amorphous solids, respectively. The result of the dissolution kinetic analysis based on the dissolution model including the phase transition showed that the dissolution behaviors of ATCH, ATC30 and ATC120 were significantly different, respectively, reflecting their intermolecular interaction in the solids. THz was able to indicate a difference between the chemical structure of amorphous solids ATC30 and ATC120, which were not able to discriminate by the XRD. • Crystalline atorvastatin Ca was transformed into amorphous solid by the grinding. • Amorphous grinding for 30 min had lower solubility than amorphous for 120 min. • X-ray diffraction profile of amorphous for 30 min was same as that for 120 min. • Terahertz spectrum of amorphous for 30 min was different from that for 120 min. • Terahertz spectrum of amorphous for 30 min was different from that for 120 min.