LAUSR

Abstract The nanomechanical properties of the &agr;‐, &bgr;‐, and &ggr;‐ conformational polymorphs of chlorpropamide were determined by the dynamic contact module continuous stiffness measurement at nanoindenter. The mechanical anisotropy of the &agr;‐polymorph was confirmed by indenting different faces, and its deformational behavior was assigned as ductile. Based on the nanoindentation results, the &bgr; and &ggr; forms are moderately hard with plastic flow at contact points. The results revealed a correlation between Young's modulus and inter‐planar interaction energy with regard to crystal orientation. Interpretation of the measurements was assisted by two‐ and three‐dimensional periodic density functional theory (DFT) calculations, yielding inter‐planar energies of polymorphs along the cell vectors and exhibiting a very good match with the experimental observations. The results suggest that the inter‐planar interaction energy could serve as a first‐order indicator for ranking the mechanical propensity of crystalline active ingredients. The study confirms the practical aspect of using the &agr;‐ form for preparing chlorpropamide tablets with a direct compression procedure due to its substantial level of ductility. Graphical abstract Figure. No Caption available.