Crystal Engineering to Design of Solids: From Single to Multicomponent Organic Materials
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Pharmaceutical materials which comprise drugs and excipients are mainly organic molecules. These materials frequently exhibit physicochemical properties that can impact formulation, manufacturing and packing processes as well as product performance and safety. In this context, crystal engineering (CE) has intensively grown in recent years as a strategy to reinvent bioactive molecules with well-known and approved pharmacological effects. It aims to improve their physicochemical properties without affecting the molecules’ intrinsic characteristics or compromising their stability. CE is based on molecular recognition involving non-covalent interactions, which in organic materials, are responsible for the regular arrangement of molecules in the crystal lattice. Modern CE encompasses any manipulation that results in an alteration of the crystal packing as well as methods that cause crystal lattice disruption, crystal size reduction or a combination of them. Nowadays, cocrystallization has been the most explore strategy to improve solubility, dissolution rate and bioavailability. However, its combinatorial nature involving two or more small organic molecules, and the use of diverse crystallization processes increase the possible outcomes. As a result, 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.