Low-molecular weight organogel matrices as crystallisation media for active pharmaceutical ingredients

The vast majority of small-molecule active pharmaceutical ingredients (APIs) are formulated in the crystalline state, for reasons including thermodynamic stability, ease of purification and characterisation, and better control over polymorphism. However, the selective crystallisation of polymorphic APIs provides a significant hurdle to overcome, especially in the case of API co-crystals. Herein we report a series of low-molecular-weight organogels (LMWGs) which can be used to selectively crystallise APIs. In solution, these LMWGs (2-10 mg mL^-1) self-assemble through hydrogen bonding to form stable gels which feature nano-structured morphologies. When utilised as crystallisation media, these LMWGs can influence crystal growth, as evidenced by the discovery of two novel 1 : 1 co-crystals of chlorzoxazone with nicotinamide and chlorzoxazone with isonicotinamide. This work highlights the potential of LMWGs as another means of controlling API crystallisation.