Chlorine K-Edge X-Ray Absorption Near-Edge Structure Analysis of Clarithromycin Hydrochloride Metastable Crystal

X-ray absorption fine structure (XAFS) spectra, especially X-ray absorption near-edge structure (XANES), show unique features depending on the chemical states and structures in the vicinity of the X-ray absorbing elements. As such, they can be used to identify the chemical environment of elements. XAFS spectroscopy was applied to investigate the chemical environment of chloride ions in a metastable form A crystal of the antibiotic clarithromycin hydrochloride hydrate. The XANES of the form A crystals showed low similarity to that of the active pharmaceutical ingredient (API) hydrochloride salt crystals, but showed a high similarity to that of a hydrochloride aqueous solution. This indicated that the chloride ion in the form A crystals predominantly interacted with water molecules and was fully hydrated, which was consistent with the previous presumption that form A may be high water-content crystals. This study demonstrated that this XAFS spectroscopy method would be a potent alternative technique for evaluating APIs.