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

• Published in: Journal of pharmaceutical sciences 2020-06, Vol.109 (6), p.2095-2099
• Main Authors: Ito, Masataka, Shiba, Rika, Suzuki, Hironori, Noguchi, Shuji
• Format: Article
• Language: English
• Subjects: Absorption spectroscopy; Crystal structure; Phase transition; Polymorph; X-ray powder diffraction
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2020.03.015

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.