Multicomponent Crystal of Mefenamic Acid and N-Methyl-d-Glucamine: Crystal Structures and Dissolution Study

A novel multicomponent crystal (MC) of mefenamic acid (MA) and N-methyl-d-glucamine (MG) had been prepared to improve the physicochemical properties of poorly soluble drugs, and was characterized for its physicochemical properties by powder X-ray diffraction analysis, differential scanning calorimetry thermal analysis, FT-IR spectroscopy, in vitro dissolution rate, and physical stability. In addition, the crystal structure was determined by single-crystal X-ray diffraction analysis. The differential scanning calorimetry thermogram of the MA-MG binary system exhibits a single and sharp endothermic peak at 151.20°C, which was attributed to the melting point of a MC of MA-MG. FT-IR spectroscopy analysis showed the occurrence of solid-state interaction by involving proton transfer between MA and MG. The crystal structure analysis confirmed that MA-MG formed 1:1 ratio salt type MC. The formation of a MC of MA with MG significantly improved the dissolution rate of MA in compared to intact MA, and also the crystal demonstrated a good stability under a high relative humidity. These good properties would be attributed to the layer structure of MA and MG in the crystal.