Rapid characterisation of the inherent dispersibility of respirable powders using dry dispersion laser diffraction

Graphical abstract

Abstract

Understanding and controlling powder de-agglomeration is of great importance in the development of dry powder inhaler (DPI) products. Dry dispersion laser diffraction measures particle size readily under controlled dispersing conditions, but has not been exploited fully to characterise inherent powder dispersibility. The aim of the study was to utilise particle size-dispersing pressure titration curves to characterise powder cohesivity and ease of de-agglomeration. Seven inhaled drug/excipient powders (beclometasone dipropionate, budesonide, fluticasone propionate, lactohale 300, salbutamol base, salmeterol xinafoate and tofimilast) were subjected to a range of dispersing pressures (0.2–4.5 Bar) in the Sympatec HELOS/RODOS laser diffractometer and particle size measurements were recorded. Particle size-primary pressure data were used to determine the pressures required for complete de-agglomeration. The latter were employed as an index of the cohesive strength of the powder (critical primary pressure; CPP), and the curves were modelled empirically to derive the pressure required for 50% de-agglomeration (DA ₅₀). The powders presented a range of CPP (1.0–3.5 Bar) and DA ₅₀ (0.23–1.45 Bar) which appeared to be characteristic for different mechanisms of powder de-agglomeration. This approach has utility as a rapid pre-formulation tool to measure inherent powder dispersibility, in order to direct the development strategy of DPI products.