Crystallization is widely employed in the pharmaceutical industry, ranging from the early stages of drug discovery and formulation to the large-scale production of pharmaceuticals. The process involves the formation of a new crystalline solid phase and can target either a solute, e.g., small molecule or protein, or the solvent, e.g., freezing of water.

The crystallization of solutes assisted by functionalized surfaces will be first discussed. Self-assembled monolayers immobilized on glass can modify the nucleation kinetics of small molecules, i.e., aspirin, and macromolecules. The role of secondary interactions between the surface and the solute was investigated through thin-film crystallization and X-Ray diffraction. Modified surfaces can also promote the formation of unknown polymorphs, thus showing the potential of this technique during the early stages of drug discovery.

The crystallization of proteins will be successively described considering diffusion-dominated environments. The elimination of convection allows better control over crystallization, promotes reproducible crystal size, and reduces the risk of crystal breakage. The use of agarose and silica gels will be presented and their advantages and limitations described, together with strategies to overcome them.

Finally, a focus on solvent crystallization will be provided. Freeze-drying is selected as a case-study as the ice crystals’ morphology impacts the freeze-dried product morphology and, consequently, the drying rate, the residual moisture, and the reconstitution time. Freezing of unit doses in vials is a complex process, and the impact of thermal interactions among vials on ice crystallization and final product morphology will be discussed by comparing experimental data and mathematical modelling.