Crystal engineering and pharmaceutical crystallization

This chapter summarizes the beginnings of supramolecular chemistry and crystal engineering from the early 1990s to the supramolecular synthon, then leading to cocrystals via heterosynthons during the past two decades. The design of multicomponent pharmaceutical cocrystals through an understanding of strong hydrogen bonds and selection of suitable coformers for the improvement of drug solubility and permeability is the main focus in this chapter. Strategies for the designed assembly of binary, ternary, and higher component cocrystals as well as salts, ionic cocrystals, and eutectics with higher pharmacokinetic profile compared with the reference drug are highlighted. The approval of cocrystal–salt drugs after 2015 has shifted efforts toward process intensification and continuous crystallization compared with batch mode for the manufacture of solid drug formulation. Several such drug forms developed through crystal engineering are on the market shelf as improved oral medicines.