Crystal Structure and Physical Properties of Loxoprofen Sodium Dihydrate

Abstract

The crystal structure and physicochemical properties of loxoprofen sodium dihydrate (LOX-Na 2hyd), a widely used antipyretic analgesic, were investigated. Single crystals were successfully prepared, and their structure was determined via single-crystal X-ray diffraction. The crystals featured alternating hydrophilic and hydrophobic layers: the hydrophilic layer contained water molecules and sodium ions forming coordination and hydrogen bonds, while the hydrophobic layer contained loxoprofen molecules. Thermal analysis revealed that LOX-Na 2hyd desolvated two water molecules at approximately 60°C, dehydrating into an anhydrate without passing through the amorphous state. This anhydrate reabsorbed moisture at approximately 25% relative humidity, reverting to the dihydrate form. Dynamic vapor sorption confirmed the stability of the dihydrate across a wide humidity range. The cyclopentanone ring in the LOX structure exhibited disorder, and crystallographic analysis indicated the coexistence of four stereoisomers (5R, 13R; 5S, 13S; 5R, 13S; 5S, 13R). These findings suggest structural flexibility and potential relevance for optical resolution. Because optical resolution enhances the efficacy of other drugs, such as omeprazole and ofloxacin, this study provides valuable structural insight to support similar applications for LOX. Overall, this work contributes foundational knowledge toward improving the stability and efficacy of LOX formulations through structural and physicochemical understanding.