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Understanding the Tabletability Differences between Indomethacin Polymorphs Using Powder Brillouin Light Scattering

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Abstract

Purpose

The unconventional tabletability of the indomethacin polymorphs – α and γ – are investigated from a topological and mechanical perspective using powder Brillouin light scattering (p-BLS) to identify the specific structure-performance relationship in these materials.

Method

Indomethacin (γ-form) was purchased and used to prepare the α polymorph. Powder X-ray diffraction was used to confirm phase identity, while p-BLS was used to obtain the mechanical properties. Energy frameworks were determined with Crystal Explorer to visualize the interaction topologies. Using a Carver press and a stress-strain analyzer, the tableting performance of each polymorph was determined.

Results

Polymorph-specific acoustic frequency distributions were observed with distinct, zero-porosity, aggregate elastic moduli determined. The p-BLS spectra for α-indomethacin display a population of low-velocity shear modes, indicating a direction of facilitated shear. This improves slip-mediated plasticity and tabletability. Our p-BLS spectra experimentally indicates that a low-energy slip system is available to α-indomethacin which supports ours and previous energy framework calculations. Despite a 2d-layered crystal motif favorable for shear deformation, the γ-form displays a higher shear modulus that is supported by our hydrogen-bonding analysis of γ-indomethacin.

Conclusion

Our experimental, mechanical data is consistent with the predicted interaction topologies and these two inputs combined permit a comprehensive, molecular understanding of polymorph-specific tabletability.

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Acknowledgments and Disclosures

B.A.Y. was supported by the Terrence and Donna Dahl Pharmaceutics Fellowship during the course of this project.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences and Experimental Therapeutics, University of Iowa, Iowa City, Iowa, 52242, USA

    Beth A. Young, Dherya Bahl & Lewis L. Stevens

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  1. Beth A. Young
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  2. Dherya Bahl
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  3. Lewis L. Stevens
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Correspondence to Lewis L. Stevens.

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Young, B.A., Bahl, D. & Stevens, L.L. Understanding the Tabletability Differences between Indomethacin Polymorphs Using Powder Brillouin Light Scattering. Pharm Res 36, 150 (2019). https://doi.org/10.1007/s11095-019-2681-9

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