Enhancing the physicochemical properties of solid-state materials through crystal engineering enables optimization of these materials without covalent modification. Cocrystals have become a reliable means to generate novel crystalline forms with multiple components and they exhibit different physicochemical properties compared to the individual components. This dissertation exemplifies methodologies to generate cocrystals of active pharmaceutical ingredients (API’s) based upon knowledge of supramolecular interactions (supramolecular synthons), while focusing on enhanced delivery through in vitro and in vivo processes with both salts and cocrystals respectively. Different multiple component crystalline entities were discovered through traditional solution based techniques and with mechanochemistry involving small amounts of an appropriate solvent, or solvent drop grinding (SDG). Dissolution studies and pharmacokinetic enhancement through optimized oral drug delivery via supramolecular complexes are presented with particular attention to non-covalent intermolecular interactions.