Nanomechanical testing in drug delivery: Theory, applications, and emerging trends

Mechanical properties play a central role in drug formulation development and manufacturing. Traditional characterization of mechanical properties of pharmaceutical solids relied mainly on large compacts, instead of individual particles. Modern nanomechanical testing instruments enable quantification of mechanical properties from the single crystal/particle level to the finished tablet. Although widely used in characterizing inorganic materials for decades, nanomechanical testing has been relatively less employed to characterize pharmaceutical materials. This review focuses on the applications of existing and emerging nanomechanical testing methods in characterizing mechanical properties of pharmaceutical solids to facilitate fast and cost-effective development of high quality drug products. Testing of pharmaceutical materials using nanomechanical techniques holds potential to develop fundamental knowledge in the structure-property relationships of molecular solids, with implications for solid form selection, milling, formulation design, and manufacturing. We also systematically discuss pitfalls and useful tips during sample preparation and testing for reliable measurements from nanomechanical testing.