Measurement of Process-Dependent Material Properties of Pharmaceutical Solids by Nanoindentation

Liao, Xiangmin; Wiedmann, Timothy S.

doi:10.1002/jps.20227

Cited by 35 publications

(27 citation statements)

References 26 publications

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“…18,24,35 Our indentation experiments were conducted on the dominant face of the crystal samples because it is believed that the dominant face plays a major role on powder compaction. Different results in particle hardness are expected from a combination of instrumentation, sample preparation, possible different crystal face and indentation size effect.…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12][13][14] With the rapid development of atomic force microscopy (AFM), AFM nanoindentation has quickly become a very promising technique to assess particle mechanical properties of pharmaceutical materials. [15][16][17][18][19][20] With little material, AFM nanoindentation provides rich information on high-resolution imaging with nanometer spatial resolution and local mechanical studies with nanoNewton forces. 21,22 Previous studies have been conducted in hopes to predict powder compaction performance using microor nanoindentation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Correlating Particle Hardness with Powder Compaction Performance

Cao

Morganti

Hancock

et al. 2010

Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Correlating Particle Hardness with Powder Compaction Performance

Cao

Morganti

Hancock

et al. 2010

Journal of Pharmaceutical Sciences

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“…Determination of mechanical particles at the single particle level can be accomplished with high-resolution instruments such as an atomic force microscope (AFM) and an instrumented nanoindenter (35)(36)(37)(38)(39). Since these measurements are influenced by surface properties, the obtained results have to be supported with complementary techniques such as high-pressure diffraction (40)(41)(42)(43) or simulation approaches based on determination of crystal interplanar d-spacings, attachment or surface energy (44)(45)(46)(47).…”

Section: How Can Mechanical Particles Be Determined In Practice?mentioning

confidence: 99%

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

2016

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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.

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“…Instrumented indentation has been used to quantify a wide variety of mechanical properties including elastic modulus [13][14][15], which may be crystal orientation-dependent [16,17], and hardness [18,19], which is often used as a surrogate for general plastic flow behavior. Additionally, yield points during initial loading can be indicative of the onset of dislocation nucleation [20].…”

Section: Introductionmentioning

confidence: 99%

Nanoindentation of HMX and Idoxuridine to Determine Mechanical Similarity

2017

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Assessing the mechanical behavior (elastic properties, plastic properties, and fracture phenomena) of molecular crystals is often complicated by the difficulty in preparing samples. Pharmaceuticals and energetic materials in particular are often used in composite structures or tablets, where the individual grains can strongly impact the solid behavior. Nanoindentation is a convenient method to experimentally assess these properties, and it is used here to demonstrate the similarity in the mechanical properties of two distinct systems: individual crystals of the explosive cyclotetramethylene tetranitramine (HMX) and the pharmaceutical idoxuridine were tested in their as-precipitated state, and the effective average modulus and hardness (which can be orientation dependent) were determined. Both exhibit a hardness of 1.0 GPa, with an effective reduced modulus of 25 and 23 GPa for the HMX and idoxuridine, respectively. They also exhibit similar yield point behavior. This indicates idoxuridine may be a suitable mechanical surrogate (or "mock") for HMX. While the methodology to assess elastic and plastic properties was relatively insensitive to specific crystal orientation (i.e., a uniform distribution in properties was observed for all random crystals tested), the indentation-induced fracture properties appear to be much more sensitive to tip-crystal orientation, and an unloading slope analysis is used to demonstrate the need for further refinement in relating toughness to orientation in these materials with relatively complex slip systems and crystal structures.

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Measurement of Process-Dependent Material Properties of Pharmaceutical Solids by Nanoindentation

Cited by 35 publications

References 26 publications

Correlating Particle Hardness with Powder Compaction Performance

Correlating Particle Hardness with Powder Compaction Performance

Application of instrumented nanoindentation in preformulation studies of pharmaceutical active ingredients and excipients

Nanoindentation of HMX and Idoxuridine to Determine Mechanical Similarity

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