Nicotine Refined: Crystal Engineering of (S)-Nicotinium Malate Salts

Nicotine, a widely consumed, yet considered toxic, active pharmaceutical ingredient for recreational use, is known to rapidly deteriorate into unwanted and potentially harmful side products. Crystallization with salt formers transforms the unstable oil into solids with tunable properties. However, previously reported salts and co-crystals are not necessarily safe for human consumption, with several containing heavily halogenated coformers. When combined with malic acid, a generally recognized as safe (GRAS) compound, the four resulting crystalline solids exhibited melting points as high as 122 °C and spanned a range of ∼30 °C. The nicotine-based materials also possessed improved degradation properties. A detailed analysis of the crystal packing and thermodynamic properties provides context for the observed properties.