Laser diffraction particle sizing of cohesive lactose powders

The objective was to develop a suitable laser diffraction particle sizing method for cohesive lactose present either as agglomerates or adhered onto coarse lactose carriers. Micronised lactose (ML) was prepared by fluid energy milling. Particle size distributions (PSD) were determined by laser diffraction (Malvern Master Sizer S, U.K.). Ethanol, propan-2-ol, 1-butanol and isooctane were selected as dispersants. Sonication for 5 min caused de-agglomeration of agglomerates initially formed in ethanol, propan-2-ol, and 1-butanol; the volume mean diameter (VMD) of ML in ethanol, propan-2-ol, and 1-butanol was 2.9 μm, 2.8 μm and 2.5 μm, respectively. Coarse lactose (Foremost 95 (F95)) showed a mono-modal distribution in all dispersants with a VMD of 117 μm in propan-2-ol. The robustness of particle sizing of ML in each dispersant was determined over time. Propan-2-ol was the most suitable dispersant for ML, as the PSD (VMD of 2.8 ± 0.3 μm) did not change over a 3 h period. In comparison, for ethanol, VMD of FL was stable only for 30 min, but then increased from 2.9 μm to 9.0 μm after 3 h. The particle size changes over time occurring in ethanol were related to dissolution of fine lactose and possible re-crystallisation with subsequent increased VMD. ML added to coarse lactose and existing as agglomerated particles or as particles adhered to the coarse lactose could be determined with the use of a carefully selected sonication time to minimise coarse lactose comminution.