A cocrystal of mefenamic acid (MA) -nicotinamide (NA) has been reported to increase the solubility of MA, but it still does not exceed the solubility of sodium mefenamate (SM). Accordingly, this research dealt with a new salt cocrystal arrangement of SM − NA. Cocrystal screening was performed, followed by powder and single-crystal preparation. Solvent drop grinding and slow evaporation at cold and ambient temperatures were employed to produce the multicomponent crystal. Two new salt cocrystals were found as hemihydrates and monohydrates, named SMN-HH and SMN-MH, respectively. SMN-MH single crystals were successfully isolated and structurally analyzed using a single crystal X-ray diffractometer. Pharmaceutical properties were investigated, including hydrate stability, solubility, and intrinsic dissolution. The experiments showed that the hemihydrate was stable under ambient humidity and temperature, and that the monohydrate rapidly changed to hemihydrate. Both hydrates improved the solubility and intrinsic dissolution of SM, but SMN-HH was superior. The data showed that SMN salt cocrystals combine the advantages of salt and cocrystals and show potential for dosage form development.

Salt and cocrystal have been reported as two main classes of the solid phase to modulate the physicochemical properties of the active pharmaceutical ingredient (API), such as increased solubility, dissolution rate, and stability. Structurally, cocrystals are composed of neutral compounds; meanwhile, salt combines the ionic components. Each solid form offers advantages and can be tailormade to gain a specific purpose. For example, cocrystals may enhance solubility and dissolution rate, but some may also decrease those parameters. On the other hand, alkaline-drug salt generally has a higher solubility than the parent drug. But how if the alkaline salt drug is combined with a similar coformer? Can it produce a salt cocrystal with superior performance?