Application of resonant acoustic mixing in the synthesis of vitamin C–nicotinamide variable stoichiometry cocrystals†

The use of resonant acoustic mixing (RAM) to synthesize variable stoichiometry cocrystals of nicotinamide and vitamin C was investigated. Liquid assisted RAM (LA-RAM) was used to generate two polymorphs, Form I and II, of the 1?:?1 cocrystal of nicotinamide and vitamin C at a 700 mg scale using ethanol and methanol respectively as the liquid additives. LA-RAM was used to scale up polymorphs I and II of the 1?:?1 cocrystal to 20 grams. Finally, LA-RAM used was to produce a high purity 3?:?1 cocrystal of nicotinamide and vitamin C when either methanol or ethanol was used as the liquid additive. LA-RAM is demonstrated to be a scalable, environmentally friendly, ball-free method to make variable stoichiometry cocrystals.