Compared to free base forms, salt forms are more frequently obtained as hydrates during solid form screening, although physically unstable hydrates are difficult to select for drug development. In this study, loxoprofen sodium dihydrate (LOXNa-2H2O), a widely used anti-inflammatory drug, was selected as a model drug to investigate the potential use of sugar as a coformer for cocrystallization with Na salts and the effect of salt cocrystallization with sugars on hydrate formation. In a screening study by liquid-assisted grinding with ethanol, two sugars, ribose (RIB) and fructose (FRU), formed new salt cocrystals with LOXNa. Differential scanning calorimetry, thermogravimetry, temperature-programmed powder X-ray diffraction, and water vapor sorption/desorption isotherm measurements revealed that the LOXNa·RIB and LOXNa·FRU salt cocrystals were a monohydrate and anhydrate, respectively. Single-crystal X-ray structural analysis of both salt cocrystals showed that direct ionic interaction did not occur between the Na cation and the carboxylate anion of LOX. Instead, sugars were coordinated around a Na cation, and a consecutive alternating structure of Na cations and sugars with a one-dimensional chain was formed along the b-axis. These characteristic chain structures prevented water molecules from approaching the Na cation and reduced the propensity for hydrate formation. FRU possesses one more hydroxyl group than the RIB molecule. The resulting strong hydrogen bonding network stabilized the LOXNa-FRU as an anhydrate without water molecules. Since sugars are safe and inexpensive excipients with various species, they can be useful coformers for salt cocrystals with various drug Na salts.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.