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How can single particle compression and nanoindentation contribute to the understanding of pharmaceutical powder compression?

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Understanding the deformation behavior of powder, including individual particle responses, is a critical factor in powder compaction, influencing powder compressibility and compactibility. Traditional approaches involve conducting powder compression experiments and applying mathematical models like the Heckel-Model to derive characteristic compression parameters. However, the physical correlation of these parameters with the deformation behavior is often not well-understood. Single particle compression and nanoindentation offer a more detailed exploration of the deformation behavior in particulate materials. In this investigation, single particle compression experiments were conducted to characterize the deformation behavior of common pharmaceutical excipients and active pharmaceutical ingredients (APIs) with various irregular particle morphologies of industrial significance. The findings were compared with results from powder compression experiments. The technique proved valuable for qualitative characterization and clarification of deformation behavior. However, the establishment of a quantitative functional relationship between single particle deformation behavior and powder compression exhibited limitations. Nanoindentation was employed as a complementary technique to characterize the micromechanical behavior of the APIs. A linear relationship was observed between median indentation hardness and material densification strength, a characteristic parameter derived from in-die powder compression analysis.
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