An overview of the application of power ultrasound to crystallization of organic molecules, and the equipment developed in recent years in which sonocrystallization and sonochemistry may be carried out at industrial scale, is presented. It includes both results from the research and development programs carried out by us and a survey of developments in the field more generally. The most important effect of ultrasound on crystallization is the induction of nucleation and the principal benefits derived from an ability to manipulate this effect. The reported effects of ultrasound on crystal nucleation and growth have been briefly reviewed, and examples are given of physical properties of the products having been manipulated by varying and controlling the insonation regime. New applications, directions, and developments have been identified. Developments in scale-up methods and available equipment have also been reviewed. It is the availability of robust large-scale equipment that has been critical to establishing the viability of this technology for industrial use in recent years.

A new and systematic method for co-crystal screening has been developed, based on improvements in the understanding of the thermodynamic factors that influence co-crystal formation. This method works from the premise that pure component solubilities determine the concentration regions to screen for new co-crystals, rather than the stoichiometry of the co-crystal. An extended phase diagram screen gives the composition ranges in which the co-crystal is the stable crystalline form. The method is based on the measurement of saturation temperatures which are experimentally easily accessible using standard laboratory equipment. The method has been validated using both carbamazepine and cinnamic acid with a number of co-formers in ethanol solvent. New co-crystals of carbamazepine with isonicotinamide, benzamide and 3-nitrobenzamide, and of cinnamic acid with 3-nitrobenzamide have been discovered.

No abstract