Phase Transformations of Azithromycin Crystals Investigated by Thermal and Spectroscopic Analyses Combined with Ab Initio Calculations

Abstract

In this research, we employed thermal analyses, X-ray diffraction, and Raman spectroscopy techniques to study the thermodynamic stability of the azithromycin dihydrate (AZM-DH) crystal and the vibrations under different temperature conditions. This study inferred that the crystal underwent two phase transformations. The first phase transformation was associated with a change from the orthorhombic symmetry to a new triclinic phase in the temperature interval of 388−395 K. The second phase transformation was characterized as a thermodynamically irreversible process from a triclinic phase to an amorphous phase, as observed for temperatures above 395 K. The new triclinic symmetry phase was accurately determined using the unit cell refinement by the Le Bail method, demonstrating that its structural system belongs to the P1̅ -space group. To the better of our knowledge, this new polymorphic phase has not been published until now. Moreover, a corrected assignment of Raman-and IR-active bands under room temperature was performed through vibrational analysis, using calculations based on density functional theory (DFT). Finally, chemical−physical properties of the AZM-DH crystal that had not been studied before are reported herein.

New polymorphic phase of arachidic acid crystal: structure, intermolecular interactions, low-temperature stability and Raman spectroscopy combined with DFT calculations

“…All bands that appeared in this wavenumber region (40-155 cm −1 ) are associated with lattice modes, which can give important information to understand the intermolecular interactions, thermodynamic stability, and physicochemical properties of organic systems, as well as polymorphism in materials in the crystalline state. 15,16,[64][65][66] According to the literature, 15 these vibration modes have coupling with hydrogen bonds belonging to dimers responsible for the crystalline lattice. The inset of Fig.…”