3D ED/MicroED-Based Structural Analysis of Ipragliflozin– l -Proline Cocrystal from Pharmaceutical Tablet

Abstract

In this study, we investigated the crystal structure of cocrystal components in tablets using 3D ED/MicroED, focusing on the ipragliflozin–l-proline cocrystal. First, by combining 3D ED/MicroED and single-crystal X-ray diffraction (SCX) analysis of the powder before tableting, we confirmed the orthorhombic crystal system and successfully determined the crystal structure of the cocrystal. Subsequently, analysis of the commercial formulation, Suglat tablet, allowed us to successfully determine the same cocrystal structure from the tablets. The crystallographic data obtained from both samples showed good agreement, supporting that the cocrystal is stably maintained during the tableting process without dissociation. Furthermore, multipoint 3D ED/MicroED measurements of the crushed tablet revealed no detectable crystalline phases corresponding to the dissociated free forms. This study demonstrates that 3D ED/MicroED, beyond serving merely as a complementary technique to SCX, enables structural analysis of crystalline phases in complex samples such as tablets and multicomponent mixtures, and further supports its practical utility for microcrystal analysis.