An approach to characterising the cohesive behaviour of powders using a flow titration aerosolisation based methodology

The purpose of this study was to characterise the cohesive behaviour of powders by measuring aerosolisation at a sequence of different flow rates, i.e. flow titration. Salbutamol sulphate and Lactohale 300 were model cohesive materials. Laser diffraction particle sizing of the aerosolised plume provided in-situ, real time particle size distributions of the aerosolised powder dispersed at increasing flow rates, from 30 to 180 L min−1. Relative de-agglomeration was determined from the cumulative particle size of the aerosolised powder less than 5.4 μm compared with the full availability of particles in that size range. Relative de-agglomeration-flow rate profiles were modelled using a non-linear least squares regression to fit an empirical 3-parameter sigmoidal equation; the parameters of the sigmoid were estimated from the data. Relative de-agglomeration–flow rate titration profiles and their estimated parameters were obtained to define the different de-agglomeration mechanisms of the two cohesive powders. Salbutamol sulphate showed a maximum percent de-agglomeration of 54.9%, compared with Lactohale 300 which was only 29.5%. Lactohale 300 gave 50% of its maximum de-agglomeration at a flow rate of 48.0 L min−1 while the equivalent for Salbutamol sulphate was 113.8 L min−1. Salbutamol sulphate and Lactohale 300 demonstrated different patterns of dispersion in relation to de-agglomeration mechanism. This approach to characterising the aerosolisation processes has significant application in designing formulation and processing strategies for pharmaceutical inhalation drug delivery.