The physicochemical properties and the performance of both active pharmaceutical ingredients (APIs) as well as new chemical entities (NCEs) can be significantly modified by converting them into different crystalline forms, including polymorphs, solvates, co-crystals and host-guest complexes. In particular, for APIs and NCEs having low aqueous solubility, and consequently poor or variable bioavailability, such solid-state modification can yield new crystal forms with enhanced solubility, facilitating the process of formulating effective pharmaceutical products. In this context, such supramolecular manipulation is recognized as a crystal engineering approach to broadening the solid-state landscape of bioactive molecules, with potential for improving not only the solubility of a drug but additional, pharmaceutically relevant properties such as thermal stability, tabletability and reduction of hygroscopicity. In this presentation, recent case studies involving the generation of multiple crystalline forms of selected APIs and NCEs and the physicochemical characterization of these products will be described. Bioactive compounds that will feature in these case studies include antioxidants, anticancer agents, antivirals, and compounds with antimalarial and anti-tubercular activities. Key methods used to identify new crystal phases unequivocally and determine their thermodynamic stability include X-ray diffraction, spectroscopic techniques and thermal analysis. The utility of single crystal X-ray diffraction in elucidating the crystal structures of such new phases at atomic resolution will be emphasized, as will the application of powder X-ray diffraction to phase identification and monitoring of phase transformations occurring at different temperatures. Assessment of drug beneficiation resulting from this crystal engineering approach will also be described. Finally, the importance of employing this type of supramolecular intervention at an early stage following drug discovery will be highlighted for its potential to identify the most favourable candidates for further development.
•An appreciation of the fact that compared to ab initio drug discovery, a crystal engineering approach to generating multiple solid forms of poorly-soluble bioactive molecules may be a shorter and relatively inexpensive route to improving pharmaceutically relevant properties.
•That characterization of new solid-state forms of bioactive compounds by X-ray diffraction techniques is essential for unequivocal classification of these forms as polymorphs, solvates, co-crystals, salts, or other molecular entities.
•Early application of crystal engineering of multi-component systems containing bioactive molecules is desirable since it enables the researcher to identify lead compounds that are amenable to supramolecular modification and hence streamlines the process of drug candidate selection.
•At the lowest level, the audience will be better prepared to understand the rapidly expanding volume of literature on the topic of multi-component systems containing drug molecules. For those interested in pursuing research on alternative solid forms of drugs with enhanced properties, the presentation will describe systematic procedures for generating and characterizing them. A more efficient way of using powder X-ray diffraction in the identification of drug complexes will also be demonstrated