Effect of Environmental Humidity on the Transformation Pathway of Nitrofurantoin Modifications During Grinding and the Physicochemical Properties of Ground Products

The effect of humidity on the physicochemical properties of nitrofurantoin anhydrate and monohydrate during grinding in a humidity-controlled system was investigated using X-ray diffraction analysis, IR spectroscopy, thermal analysis and scanning electron microscopy. Anhydrate and monohydrate were transformed into a noncrystalline solid and a stable monohydrate, respectively, during grinding in a closed system. During grinding in an open system, in which the humidity level of the air was controlled (5, 50 and 75% r.h.), the anhydrate absorbed moisture from the supplied air and water content was increased at 75% r.h.; thereafter the compound was transformed into monohydrate II. The anhydrate did not absorb at 5 or 50% r.h. and was transformed into a noncrystalline solid. Monohydrate I desorbed crystal water during grinding at 5% r.h. and was transformed into a noncrystalline solid. However, monohydrate I was transformed into monohydrate II at 50 and 75% r.h. without desorption of crystal water. These results suggest that the solid-state transformation of nitrofurantoin during grinding depends upon the environmental humidity.