Solid-State Phase Transition Of Agomelatine-Phosphoric Acid Molecular Complexes Along The Salt-Cocrystal Continuum: Ab Initio Powder X-Ray Diffraction Structure Determination And Dft-D2 Analysis

The solid-state phase transition of a multicomponent active pharmaceutical ingredient (M-APIs), composed of (1:1) agomelatine and phosphoric acid (AGL-P), is characterized using a set of complementary techniques: in situ variable temperature powder X-ray diffraction (VT-PXRD), thermal analysis, spectroscopic techniques, and hot stage microscopy (HSM). It is observed that these dimorphic forms (AGL-P RT-form and HT-form) are enantiotropic and reversible in nature. The salt-cocrystal continuum of this system is demonstrated using ab initio powder XRD structure determination (SDPD) and dispersion corrected density functional theory (DFT-D2) analysis. Furthermore, this solid-state phase transition can be inferred as a martensitic-like transformation, where simultaneous proton migration and small conformational switching trigger the concerted molecular displacements of entire layers, leading to microscopic crystal contraction.