Crystal engineering to design of solids: From single to multicomponent organic materials

Primarily composed of organic molecules, pharmaceutical materials, including drugs and excipients, frequently exhibit physicochemical properties that can affect the formulation, manufactur-ing and packing processes as well as product performance and safety. In recent years, researchers have intensively developed Crystal Engineering (CE) in an effort to reinvent bioactive molecules with well-known, approved pharmacological effects. In general, CE aims to improve the physico-chemical properties without affecting their intrinsic characteristics or compromising their stability. CE involves the molecular recognition of non-covalent interactions, in which organic materials are responsible for the regular arrangement of molecules into crystal lattices. Modern CE, encompasses all manipulations that result in the alteration of crystal packing as well as methods that disrupt crystal lattices or reduce the size of crystals, or a combination of them. Nowadays, cocrystallisation has been the most explored strategy to improve solubility, dissolution rate and bioavailability of Active Pharmaceutical Ingredients (API). However, its combinatorial nature involving two or more small organic molecules, and the use of diverse crystallisation processes increase the possible outcomes. As a re-sult, numerous organic materials can be obtained as well as several physicochemical and mechanical properties can be improved. Therefore, this review will focus on novel organic solids obtained when CE is applied including crystalline and amorphous, single and multicomponent as well as nanosized ones, that have contributed to improving not only solubility, dissolution rate, bioavailability permeability but also, chemical and physical stability and mechanical properties.