Structure-mechanics and improved tableting performance of the drug-drug cocrystal metformin:salicylic acid

Abstract

Drug-drug cocrystals (DDC) represent a unique subset of pharmaceutical materials offering distinct advantages in combination therapies, pharmacokinetics, and patient compliance. However, their structure–function relationships are rarely reported despite its central importance in successful medicine. A material-sparing approach consisting of a molecular and structural perspective is reported to evaluate tabletability of a model DDC, metformin:salicylic acid, relative to its components: metformin HCl (MET) and sodium salicylate (SAL). MET alone displayed a very poor tabletability, which could be attributed to its isotropic and stiff interaction topology. SAL displayed a highly anisotropic interaction topology with layers of strongly hydrogen-bonded salicylate molecules promoting deformation and tabletability. This is also confirmed by its low moduli. DDC yielded intermediate stiffness and elastic anisotropy material with an improved plastic flow and overall better tabletability. Overall, DDC is a promising therapeutic class requiring the physical–mechanical evaluation to assure their processability to enjoy their therapeutic advantages.