Cocrystallisation by freeze-drying: preparation of novel multicomponent crystal forms

We demonstrate the utility of freeze-drying as a general method for cocrystal synthesis as well as for the preparation of new solid forms of drug-coformer cocrystal systems. Using this approach, several previously reported cocrystal phases containing pharmaceutical compounds were reproduced. In addition, a novel solid solution of caffeine and theophylline and a potential new crystal form of the theophylline:oxalic acid cocrystal were prepared. It is shown that cocrystal formation proceeds via an amorphous phase which is generated as solvent sublimes during the freeze-drying process. The application of freeze drying to cocrystallisation is advantageous as it avoids problems caused by differences in the solubilities of coformers, and is a technique which is widely used to prepare products on an industrial scale, such as in the manufacture of pharmaceutical dosage form