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Re-visitation of Two Models for Predicting Mechanically-Induced Disordering after Cryogenic Impact Milling

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Abstract

Purpose

To compare the prediction accuracy of two models used to characterize the complete disordering potential of materials after extensive cryogenic milling.

Methods

Elastic shear moduli (μs) were simulated in silico. Comparison with available literature values confirmed that computations were reasonable. Complete disordering potential was predicted using the critical dislocation density (ρcrit) and bivariate empirical models. To compare the prediction accuracy of the models, each material added for dataset expansion was cryomilled for up to 5 hr. Mechanical disordering after comminution was characterized using PXRD and DSC, and pooled with previously published results.

Results

Simulated μs enabled predictions using the ρcrit model for 29 materials. This model mischaracterized the complete disordering behavior for 13/29 materials, giving an overall prediction accuracy of 55%. The originally published bivariate empirical model classification boundary correctly grouped the disordering potential for 31/32 materials from the expanded dataset. Recalibration of this model retained a 94% prediction accuracy, with only 2 misclassifications.

Conclusions

Prediction accuracy of the ρcrit model decreased with dataset expansion, relative to previously published results. Overall, the ρcrit model was considerably less accurate relative to the bivariate empirical model, which retained very high prediction accuracy for the expanded dataset. Although the empirical model does not imply a mechanism, model robustness suggests the importance of glass transition temperature (Tg) and molar volume (Mv) on formation and persistence of amorphous materials following extensive cryomilling.

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  1. School of Pharmacy and Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, 422C Mellon Hall, Pittsburgh, PA, 15282, USA

    Mustafa Bookwala & Peter L. D. Wildfong

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  1. Mustafa Bookwala
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Bookwala, M., Wildfong, P.L.D. Re-visitation of Two Models for Predicting Mechanically-Induced Disordering after Cryogenic Impact Milling. Pharm Res 40, 2887–2902 (2023). https://doi.org/10.1007/s11095-023-03569-y

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