Crystal form selectivity by humidity control: the case of the ionic co-crystals of nicotinamide and CaCl2

Post-synthesis (de)hydration techniques were used here to explore further hydrated forms of ionic co-crystals (ICCs) of nicotinamide with CaCl2. Humidity is shown to be a crucial factor for ICCs, which cannot be ignored for a complete polymorph screening of this class of compounds. The exposure of nicotinamide[middle dot]CaCl2[middle dot]H2O obtained by kneading reaction to a controlled relative humidity of 75% led to the formation of a new hydrated phase: nicotinamide[middle dot]CaCl2[middle dot]4H2O. When nicotinamide[middle dot]CaCl2[middle dot]H2O was exposed to a relative humidity between 32% and 54%, nicotinamide2[middle dot]CaCl2[middle dot]2H2O was obtained. The anhydrous form was achieved as the result of overnight dehydration of nicotinamide[middle dot]CaCl2[middle dot]H2O at 150 [degree]C. The tetrahydrate form cannot be obtained as a first product for kinetic (or thermodynamic) reasons. Control of the relative humidity has proven to be an efficient way to selectively isolate and stabilize powders of pure hydrous ICC phases, which is fundamental for industrial applications. Crystalline structures of nicotinamide[middle dot]CaCl2[middle dot]4H2O and anhydrous nicotinamide[middle dot]CaCl2 were determined by powder diffraction.