Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients # Nanoindentation allows quantitative determination of a material's response to stress such as elastic and plastic deformation or fracture tendency. Key instruments that have enabled great advances in nanomechanical studies are the instrumented nanoindenter and atomic force microscopy. The versatility of these instruments lies in their capability to measure local mechanical response, in very small volumes and depths, while monitoring time, displacement and force with high accuracy and precision. This review highlights the application of nanoindentation for mechanical characterization of pharmaceutical materials in the preformulation phase (primary investigation of crystalline active ingredients and excipients). With nanoindentation, mechanical response can be assessed with respect to crystal structure. The technique is valuable for mechanical screening of a material at an early development phase in order to predict and better control the processes in which a material is exposed to stress such as milling and compression.

The results confirm the idea that the intrinsic mechanical properties of pharmaceutical crystals (Young's modulus) largely control and anticipate their deformational behavior during tablet compression. Young's modulus and indentation hardness represent a very valuable and effective tool in preformulation studies for describing materials' mechanical attributes, which are important for technological processes in which materials are exposed to deformation.

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