Mechanical Characterization of Pharmaceutical Powders by Nanoindentation

We would like to thank our valued customers at Chiesi Farmaceutici for sharing a recent publication with us. As part of their research in the MDPI journal Pharmaceutics, Chiesi scientists have used their NanoTest Vantage instrument to show an excellent correlation of the mechanical properties of pharmaceutical crystals as measured by nanoindentation, and their milling behaviour.

The study further validates the use of nanoindentation as a tool for the prediction of how efficiently a pharmaceutical crystal can be milled in to a powder. This methodology has been used in the pharmacuetical sector for some time now and this new work by Chiesi further extends the range of APIs and excipients for which is valid.

Nanoindentation is used to measure the mechanical properties, including hardness and Young’s modulus, of individual crystals. The nanoindentation process can also be used to drive cracking in the sample material. Once the crack lengths have been quantified the fracture toughness (Kc) of the material may be determined. With hardness (H) and Kc  both known the “brittleness index” (b) may be determined using the below equation:

The higher the b value the more easily cracks will initiate and propagate and as such it is a useful predictor of how “grindability” or “millability” of the sample material. Conversely lower values would imply a much more ductile response and it follows that particle size reduction would be more challenging.

(a) Mechanical hysteresis curves for sodium chloride (green) and lactose (yellow); black arrows indicate step-like features in the ascendant part of the loop due to crack propagation. (b) Grindability index as a function of the brittleness index b
(Mechanical Characterization of Pharmaceutical Powders by Nanoindentation and Correlation with Their Behavior during Grinding. Pharmaceutics 2022, 14, 1146.)

Grindability index as a function of the brittleness index b is shown in the figure above (b). In most cases a good correlation between the two indices is evident. Grindability index is determined from measurements of the dv90 at different milling times.

Download the open access paper here.

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