*3.1. Supramolecular Processes in Crystal Growth*

Nucleation is a molecular assembly process, where a critical number of molecules are needed to achieve a phase change from the liquid melt or solution to form a crystalline solid. The driving force for achieving the critical point of molecular assembly is linked to the free energy of the process [6]. For solution-based crystallisation, which is predominantly used in processing API, the free energy required is linked to the solubility behaviour of the material in a specific solvent. The magnitude of the difference in solubility exhibited by the molecules that are crystallising from a completely solubilised state at a specified composition and temperature drives the process. The larger the differential between solubilised state and the equilibrium state, the greater the supersaturation. The resultant growth of a crystal is dependent on the solubility behaviour and any competing nucleation, which may also be taking place because of the degree of supersaturation achieved. It is, therefore, this phase change process that distinguishes crystallisation from dissolution [63,64].
