Herein is presented a report on the study of a low-solubility active pharmaceutical ingredient (API), Leflunomide (LEF). Novel multi-component systems, both pharmaceutically and non-pharmaceutically acceptable, of LEF have been synthesised. Their multi-component nature was confirmed, and each system has been comprehensively characterised using X-ray Powder Diffraction (XRPD), Single-Crystal X-ray Diffraction (SCXRD) and detailed structural analysis.A cocrystal design approach, using judicious selection of coformers based upon crystal-engineering principles was taken for the cocrystal screening process. This resulted in five new cocrystal systems, four of which are pharmaceutically acceptable. All pharmaceutically acceptable cocrystals were subjected to a comprehensive evaluation of their physicochemical properties, such as thermal properties, stability, dissolution rate and solubility. These were performed alongside that of LEF, in order to compare the physicochemical behaviour of the cocrystals with their parent API. This been performed using a variety of techniques, including DSC, TGA, DVS, XRPD, HPLC, and FTIR.The two most promisingly performing cocrystals were then selected for further experimental formulation studies alongside complementary molecular dynamics simulations; providing a combined approach to probe the relationship between cocrystal-excipient interactions in water and the associated factors determining the dissolution properties of cocrystal formulations. These formulations, with the excipients lactose (LAC) or dibasic calcium phosphate (DCP), were experimentally evaluated for their dissolution rates and solubilities; properties which appeared to be influenced by their formulation. The parameters deduced from MD simulations, such as solvent accessible surface area (SASA), intermolecular hydrogen bonds among formulation ingredients and water, and interaction energy between the API (or cocrystal) and water were found to be essential indicators of cocrystal formulation dissolution performance.In order to strengthen the understanding of the impact of intermolecular and interparticular interactions on their physicochemical behaviour, the cocrystals subjected to formulation studies were also analysed through quantum crystallographic studies. Their related intermolecular interaction energies provide experimental insight into the role cocrystallisation plays in influencing solid-state stability, and therefore physicochemical performance.This was performed via theoretical computational calculations, using PIXEL and Crystal Explorer, of intermolecular interaction energies and their individual energetic contributions to relate these properties to structural assembly and physicochemical properties.