API co-crystals - Trends in CMC-related aspects of pharmaceutical development beyond solubility

Whereas pharmaceutical co-crystals are widely described as tool to improve solubility and dissolution behavior of poorly soluble drugs, so far less focus has been on their potential role to facilitate pharmaceutical manufacturability. This review summarizes recent developments in co-crystal research regarding new trends in co-crystal preparation routes and control of solid-state material attributes. Also, recent literature was reviewed to assess risks for co-crystals in formulation processes. A growing number of publications suggest that co-crystals show potential to specifically improve mechanical properties such as tabletability and compressibility, which can often be linked to intrinsic features of crystal structure properties. However, such trends must be treated with care, as molecular structures in reported co-crystal studies are not representative in some structural parameters governing also solid-state behavior (smaller molecular weight, more balanced hydrogen bond donor versus acceptor counts) compared to recent market approved small molecule drugs.