Procainium Acetate Versus Procainium Acetate Dihydrate: Irreversible Crystallization of a Room-Temperature Active Pharmaceutical-Ingredient Ionic Liquid upon Hydration

Anhydrous procainium acetate is a room temperature ionic liquid (T-g = -25 degrees C); however, in the presence of water, this salt forms a crystalline dihydrate (T-m = 52 degrees C) that cannot be dehydrated without decomposition. Unintended crystallization of any active pharmaceutical ingredient can dramatically alter its solubility and bioavailability, making it essential that ionic liquid APIs be carefully studied for their crystallization behavior.