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

The deformation behaviour of a powder and, thus, of the individual particles is a crucial parameter in powder compaction and affects powder compressibility and compactibility. The classical approach for the characterization of the deformation behaviour is the performance of powder compression experiments combined with the application of mathematical models, such as the Heckel-Model, for the derivation of characteristic compression parameters. However, the correlation of these parameters with the deformation behaviour is physically often not well understood. Single particle compression and nanoindentation enables the in-depth investigation of the deformation behaviour of particulate materials. In this study, single particle compression experiments were performed for the characterization of the deformation behaviour of common pharmaceutical excipients and active pharmaceutical ingredients (APIs) with various, irregular particle morphologies of industrial relevance and the findings are compared with the results from powder compression. The technique was found useful for the characterization and clarification of the qualitative deformation behaviour. However, the derivation of a quantitative functional relationship between single particle deformation behavior and powder compression is limited. Nanoindentation was performed as complementary technique for the characterization of the micromechanical behavior of the APIs. A linear relationship between median indentation hardness and material densification strength as characteristic parameter derived by in-die powder compression analysis is found.