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

Abstract

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.