Influence of mechanical properties on impact fracture: Prediction of the milling behaviour of pharmaceutical powders by nanoindentation

Meier, M.; John, Edgar; Wieckhusen, Dierk; Wirth, W.; Peukert, Wolfgang

doi:10.1016/j.powtec.2008.05.009

Cited by 104 publications

(59 citation statements)

References 32 publications

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“…2-20 μm, but their thickness was relatively uniform at about 1-2 μm. While the overall shapes of AD raw material (Figure 2a,b) somewhat resembled the AD/GLU crystals, its individual crystals appeared thinner In general, the breakage of particles during milling is related to the maximum fracture energy, Young's modulus, Poisson ratio, hardness as well as initial particle size [17,18]. Fundamentally, these materials properties originate from the intermolecular interactions that govern the crystal structures and determine responses when subject to mechanical stress [14,19].…”

Section: Cocrystal Formationmentioning

confidence: 96%

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

2015

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Liquid-assisted grinding was employed to generate a cocrystal of adefovir dipivoxil (AD) and glutaric acid (GLU), which had not been successfully obtained through solution crystallization. The cocrystal formation was confirmed with powder X-ray diffraction, and its thermal stability and release behavior were studied through differential scanning calorimetry and dissolution experiments, respectively. The AD/GLU cocrystal was less stable than neat AD phase and the previously reported AD cocrystals with other dicarboxylic acids, such as suberic acid and succinic acid. This suggests that the intermolecular interactions of the AD/GLU cocrystal are probably weaker than the other crystal phases. The release behavior of the AD/GLU was comparable with the cocrystal with suberic acid. The current study verifies the effectiveness of the liquid-assisted grinding for the preparation of the thermodynamically less stable cocrystal phase.

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Section: Cocrystal Formationmentioning

confidence: 96%

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

2015

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“…Tests evaluating the mechanical properties on compacts include bending (three-and four-point), microindentation and compression tests (3)(4)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). The main characteristics of mechanical characterization on compacts are the following: the materials have already been deformed during sample preparation; a large amount of materials is needed for formation of compacts; mechanical properties of particle assembly are determined (30)(31)(32)(33)(34).…”

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

confidence: 99%

“…where x v is a calibration constant of the indenter, a is the indent diagonal, l is the length of a crack, E is Young's modulus, H is hardness, P is load, and c is the crack radius given by a + l (16,33,86,87). …”

Section: Fracture Behaviormentioning

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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“…Additionally, yield points during initial loading can be indicative of the onset of dislocation nucleation [20]. Finally, indentation-induced fracture [21][22][23][24][25][26] has been used by many researchers as a surrogate to quantify toughness in materials where meeting American Society for Testing and Materials (ASTM) standard specimen geometries would be challenging. Elastic modulus, hardness, and yield behavior are often measured using a Berkovich indenter probe, but more acute probes, such as the cube corner geometry, can be useful in initiating fracture.…”

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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Influence of mechanical properties on impact fracture: Prediction of the milling behaviour of pharmaceutical powders by nanoindentation

Cited by 104 publications

References 32 publications

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

Liquid-Assisted Grinding to Prepare a Cocrystal of Adefovir Dipivoxil Thermodynamically Less Stable than Its Neat Phase

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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