Experimental and theoretical investigation of five mosapride forms

Abstract

Mosapride (Mosa) is an active pharmaceutical ingredient commonly used for the treatment of gastroesophageal reflux disease. The purpose of this study is to investigate the possibility of discovering novel solid forms of Mosa that may arise during the process of drug product development, and subsequently analyze their structure. Five forms are obtained here: one is Mosa monohydrate, which has been reported before, and four are new forms (Mosa anhydrate, Mosa methanol hydrate (1:1:1), Mosa ethanol hydrate (1:1:1), and Mosa DMSO solvate (1:1)). The phase composition of the forms was analyzed by powder X-ray diffraction, thermal analysis, and FTIR analysis. The crystal structures of all five forms were successfully solved using single-crystal X-ray diffraction. To investigate the characteristics of five forms, a combination of X-ray crystallography, 13C solid-state nuclear magnetic resonance, molecular electrostatic potential surface, and Hirshfeld surface analysis methods were employed. It's demonstrated that the conformation of Mosa was changed due to the introduction of solvates. The water molecules play vital roles in the formation of Mosa solvates. The presence of water during the preparation process can result in different forms. Furthermore, DVS data demonstrate that the stability of Mosa solvates was significantly impacted by relative humidity.