Nanomechanical Properties of Selected Single Pharmaceutical Crystals as a Predictor of Their Bulk Behaviour

作者：Egart Mateja; Jankovic Biljana^*; Lah Nina; Ilic Ilija; Srcic Stanko

来源：Pharmaceutical Research, 2015, 32(2): 469-481.

DOI：10.1007/s11095-014-1475-3

• Single crystal
• Crystallography
• Instrumented nanoindentation
• Crystal mechanical properties
• Bulk mechanical properties

Purpose The main goal of this research was to assess the mechanical properties of APIs' polymorphic forms at the single-crystal level (piroxicam, famotidine, nifedipine, olanzapine) in order to predict their bulk deformational attributes, which are critical for some pharmaceutical technology processes.
Methods The mechanical properties of oriented single crystals were determined using instrumented nanoindentation (continuous stiffness measurement). All polymorphic forms investigated were previously identified using a combination of calorimetric and spectroscopic techniques.
Results Mechanical properties such as Young's modulus and indentation hardness were consistent with the molecular packing of the polymorphic forms investigated with respect to crystal orientation. For mechanically interlocked structures, characteristic of most polymorphic forms, response of single crystals to indentation was isotropic. The material's bulk elastic properties can be successfully predicted by measuring Young's modulus of single crystals because a good linear correlation with a bulk parameter such as the tablets' elastic relaxation index was determined.
Conclusions 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.

• 出版日期2015-2