Two-Component Pharmaceutical Cocrystals Regulated by Supramolecular Synthons Comprising Primary N···H···O Interactions

Abstract

The fundamental research focusing on structural characterizations of drug substances has been developed greatly over the past decade, which has aroused extensive interest in manipulation of enhanced physical properties of drug substances. In this context, the cocrystallization technique has been effectively applied to optimize solid forms of active pharmaceutical ingredients (APIs), which decide the physicochemical properties, i.e., stability and solubility, of compound medicines on the molecular level. This Perspective focuses on two-component pharmaceutical cocrystals of APIs regulated by supramolecular synthons comprising primary N···H···O interactions, in terms of the synthetic methodology, supramolecular cocrystallization, polymorphism and solvatomorphism, cocrystal growth kinetics, etc. Special attention is paid to supramolecular assembly of APIs based on the stoichiometric ratio, functional group effect, and competing reactions of coformers that are well-defined thanks to the increasing knowledge o...