Total Surface Energy Distributions Determined Using Inverse Gas Chromatography at Finite Dilution for Understanding the De-agglomeration of Lactose Powders

Purpose: This study determined total surface energy distributions using an Inverse Gas Chromatography (IGC) to understand the de-agglomeration of fine lactose powders commonly used in dry powder inhaler formulations. Methods: The particle size distribution (PSD) of two lactose samples, Lactohale 300 (Lac A) and micronized lactose (Lac B), were determined by laser diffraction in liquid media, and the PSD of the aerosolised plume dispersed from a Rotahaler was determined by a Spraytec at air flow rates of 30-180 l/min. The total surface energy distribution profiles were determined at finite dilution by IGC. Results: The mean diameters of Lac A and Lac B were 2.9 ± 0.2 and 3.9 ± 0.3 μm, respectively. The total surface energy of Lac A was lower than Lac B over around 3% of surface coverage. De-agglomeration profiles of the lactose samples showed that, while the percent volume less than 5.4 μm of Lac A was greater than Lac B at the air flow rates up to 90 l/min, the de-agglomeration capacity of Lac B was higher at flow rates of 120-180 l/min. These data were consistent with a surface energy and particle size-driven de-agglomeration at low flow rates and a more structure-driven de-agglomeration at higher flow rates. Conclusion: The study reinforced the importance of packing fraction, particle size and surface energy in understanding de-agglomeration of cohesive powders. However, where particles were strongly bound to give non-dispersible agglomerates, de-agglomeration was more reliant on powder structures than on surface energy.