Identification of inter-particular forces by atomic force microscopy and how they relate to powder rheological properties measured in shearing tests

• Atomic force microscopy was used to measure cohesion forces in pharmaceutical powder.
• Results were compared to cohesion measurements taken with a shear tester.
• A strong correlation between AFM and shear measurements is shown.
• Capillarity is the main source of cohesion between the single particles tested.
• Water absorption impacts powder rheology by modifying capillarity.

In this study, we used atomic force microscopy (AFM) to measure and identify the nature of the forces acting between single pharmaceutical powder particles, namely a crystalline and a semi-crystalline form of lactose. The experiments done at different moisture level, namely from 20% to 60% of relative humidity, identified capillarity as the main source of adhesion between single particles. A strong correlation was observed between the AFM adhesion results and cohesion measurements taken with a FT4 torsional type powder shear tester. This correlation between adhesion and cohesion allows the identification of capillary forces as the main source of the cohesion measured in shearing experiments in ambient moisture conditions. In the case of the semi-crystalline lactose powder, a sharp decrease in both the adhesion and cohesion at 50% RH was linked to absorption of water accumulated at the particle surfaces to fuel a phase transition of the non-crystalline domains to crystalline lactose, hence limiting the capillary action between particles at this specific moisture condition.

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