Mechanistic Understanding of Solid–Solid Phase Transition Based on In Situ Single-Crystal-to-Single-Crystal Transformations: A Case Study of AZD5462

Polymorphism in active pharmaceutical ingredients is
a critical
factor influencing their physicochemical properties and performance
in pharmaceutical applications. This study investigates the polymorphic
solid–solid phase transition of a single crystal of AZD5462,
a novel oral agonist of relaxin family peptide receptor 1 (RXFP1),
being developed for the treatment of cardiorenal diseases. Utilizing
in situ single-crystal-to-single-crystal (SCSC) transformations, we
investigated the structural changes occurring between polymorphs within
an enantiotropic system. Various analytical techniques, including
thermal analysis and X-ray diffraction, were also employed to characterize
these transitions. The results revealed a reversible phase transition
between AZD5462 Form A and Form G, driven by temperature-induced crystal
and molecular conformational changes. This highlights the potential
of SCSC transformations as a valuable tool in the study of polymorphic
behavior in pharmaceutical compounds, offering a deeper mechanistic
understanding that can facilitate the understanding of polymorphic
transformation.