Direct correlation among crystal structure, mechanical behaviour and tabletability in a trimorphic molecular compound

Bag, Partha Pratim; Chen, Miles; Sun, Changquan Calvin; Reddy, C. Malla

doi:10.1039/c2ce25100k

Cited by 107 publications

(109 citation statements)

References 17 publications

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“…[1][2][3][4][5][6][7][8] These applications demand a good understanding of their structuremechanical property relationship, which however remained relatively unexplored. [9][10][11] For example, in organic ferroelectrics, thermal or mechanical stability is a typically encountered problem that needs to be overcome for future device applications.…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanics of elastic and bendable caffeine co-crystals

Chen

Ghosh

Reddy

et al. 2014

Phys. Chem. Chem. Phys.

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Complementing recent experimental results, here we report a computational study of remarkably flexible, elastically bendable caffeine cocrystals (cocrystal solvate 1), formed from caffeine (CAF), 4-chloro-3-nitrobenzoic acid (CNB), and methanol, and compare with its unsolvated brittle form, 1 (dry). We show that 1 is able to maintain stable cocrystal structures at temperatures between 100 K and 400 K. The tensile and compressive Young's modulus of 1 are close to ~10 GPa. The ultimate strength is more than 600 MPa in tensile and 400 MPa in compressive at temperature of 100 K. The simulation results of the structural and mechanical properties of 1 are in good agreement with our previous experimental work. Notably, before the ultimate tensile stress, the stress-to-strain curves of 1 show linear behavior, but 1 (dry) show nonlinear behavior. This study might explain the remarkable elasticity of 1 and is relevant to the design of high-performance organic materials with excellent self-healing or efficient stress dissipating properties.

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Section: Introductionmentioning

confidence: 99%

Molecular mechanics of elastic and bendable caffeine co-crystals

Chen

Ghosh

Reddy

et al. 2014

Phys. Chem. Chem. Phys.

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“…(a) Mechanical properties such as hardness and fracture toughness of active pharmaceutical ingredients (APIs) play a dominant role in the context of drug manufacturing. [11][12][13][14][15][16][17][18][19][20] Hence, there is always interest in the crystal structuremechanical property correlations of APIs. (b) Understanding of the mechanical properties of metal organic framework (MOF) materials [21][22][23][24][25] and other organic crystals [26][27][28][29][30][31][32][33][34][35] can help in the design of advanced materials with overall mechanical robustness or specific property such as highly flexible crystals.…”

Section: Introductionmentioning

confidence: 99%

Temperature Dependence of Mechanical Properties in Molecular Crystals

Mohamed

Mishra

Al-Harbi

et al. 2015

Crystal Growth & Design

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Quantitative evaluation of the mechanical behavior of molecular materials by nanoindentation technique has gained prominence recently. However, all the reported data has been on room temperature properties despite many interesting phenomena observed in them with variations in temperature. In this paper, we report the results of nanoindentation experiments conducted as a function of temperature, T, between 283 and 343 K, on the major faces of three organic crystals: saccharin, sulfathiazole (form 2), and L-alanine, which are distinct in terms of the number of strength of intermolecular interactions in them. Results show that elastic modulus, E, and hardness, H, decrease markedly with increasing T. While E decreases linearly with T, the variations in H with T are not so, and were observed to drop by ~50% over the range of T investigated. The slope of the linear fits to E vs. T the organic crystals was found to be around 1, which is considerably higher than the values of 0.3 to 0.5 reported in literature for metallic, ionic and covalently bonded crystalline materials. Possible implications of the observed remarkable changes in H for pharmaceutical manufacturing are highlighted.

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“…In addition, the strength of the tablets is expected to be directly proportional to the strength of intermolecular interactions across the lowest energy slip plane in the crystal. This could be exploited to identify more efficient API formulation and manufacture (113).…”

Section: Nanoindentation In Prediction Of Bulk Mechanical Propertiesmentioning

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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Direct correlation among crystal structure, mechanical behaviour and tabletability in a trimorphic molecular compound

Cited by 107 publications

References 17 publications

Molecular mechanics of elastic and bendable caffeine co-crystals

Molecular mechanics of elastic and bendable caffeine co-crystals

Temperature Dependence of Mechanical Properties in Molecular Crystals

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

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