Multicomponent crystallisation is a widely studied technique in pharmaceutical chemistry to enhance physical properties of API’s without chemically modifying the drug moiety itself. Such crystal systems can display superior properties such as solubility, stability and bioavailability and as such many API’s are formulated as salts with several co-crystal preparations also approved for use. Methods to produce multicomponent crystals are varied with solution crystallisation being the predominant method. Crystal morphologies also influence an API’s properties with needle shaped crystals dissolving slower and possess poor flow properties compared to a more equant block shape.

In this study, we develop a method for the production of multicomponent crystals via cosublimation. Samples are sublimed on a laboratory scale from both ends of standard 15 x 160 mm test tubes sealed under vacuum with two heaters were used to equalize the sublimation rates of the components. We have shown that a range of multicomponent pharmaceutical crystals can be prepared where the components have quite different sublimation rates and that for the first time, tailor made additives can be used to obtain unprecedented morphology control of gas phase crystal growth. Dramatic changes were observed in morphology from the gas phase in sharp contrast to morphology changes in solution which produce much more modest effects. Salt formation was observed to occur during gas phase crystallisations in accordance with the pKa rule of 3 and modelling studies were carried out to understand the nature of proton transfer in these crystals in the absence of a solvent. In addition, we have shown that in addition to binary systems, ternary crystals can also be obtained via this technique.