| In early development, pharmaceutical formulation scientists are often faced with challenges of developing robust and scalable formulations in extremely stringent timelines based on limited API quantities. Hence, tablet formulation development would benefit significantly from tools that enable predictive analysis based on limited quantities of API to enable selection of excipients with appropriate physico-mechanical properties that would result in robust and scalable formulations.;With the recent technological advances, especially in sensor technologies, tools such as the compaction simulator, and instrumented nanoindentation offer hitherto unavailable means of assessing material properties with limited quantities. The goal of this work was to evaluate the physico-mechanical properties of selected pharmaceutical excipients and active pharmaceutical ingredients using a macro-scale analysis technique (compaction simulator), and a micro-scale analysis technique (nanoindentation tester) and compare the results obtained from these techniques in order to determine whether a rank order correlation exists between the two. Excipients representing diverse physic-mechanical properties, and a group of APIs were selected for the study.;For the compaction simulator studies, tablets were uniaxially compressed using a flat faced 11.28mm round tooling on the STYLCAM® 200R compaction simulator, to a target final porosity at two different cam speeds (5 rpm and 25 rpm). The force displacement profiles, plastic, elastic, and total compression energies, plasticity index, energy density and the Heckel plots were determined for each compact. These compacts were further analyzed with a Berkovich geometry indenter. The plasticity index, hardness, elastic modulus, as well as creep and relaxation were determined from the force-displacement profiles. The nature of force-displacement curves was studied to differentiate compounds based on predominant mechanisms of deformation. Compaction simulator was able to rank order the selected compounds based upon their established physic-mechanical properties. Further, the nanoindentation analysis suggests that characterization of excipients and compounds correlated well with their known mechanisms of deformation and with the process parameters (e.g. compression dwell time). These results demonstrate that nanoindentation can be potentially employed in early formulation development, to understand the physico-mechanical properties of active pharmaceutical ingredients and predict their compaction behavior. Lastly, a rank-order correlation was observed between the two techniques suggesting that either technique can be employed to get valuable insights into the properties of APIs, to help speed up the development process. |
