Development of a laser diffraction method for the determination of the particle size of aerosolised powder formulations

Abstract

Impactor data are an essential component of marketing authorisation for new dry powder aerosol formulations. However such data are time-consuming to obtain and therefore impede the rapid screening of pilot formulations. In this phase of development it would be of considerable benefit to employ a technique where data acquisition was more rapid, such as laser diffraction, to predict the fine particle fraction. It was the aim of this study to investigate whether this is a feasible premise. Five different formulations were prepared, each containing 1.5% (w/w) micronised salbutamol base (volume median diameter: 2.42 μm) blended with the sieved fraction (63–90 μm) of one of the following sugars: regular crystalline lactose, spray dried lactose “Zeparox™”, sorbitol, maltose and dextrose monohydrate. A Perspex™ box was constructed to contain particles released from a glass inhaler and allow the particles to be measured by laser diffraction at different flow rates. After being validated using monodisperse aerosols, this assembly was then employed to measure the particle size distributions of each powder formulation and its respective sugar carrier at flow rates ranging from 28.3 to 100 l min −1. Aerodynamic particle size distribution of salbutamol base from each formulation was also measured after aerosolisation at 28.3 l min −1 from the glass inhaler into an Andersen cascade impactor. The flight of monodisperse particles with diameters (2–6 μm) in the desired size range of dry powders for inhalation could be contained and the size distribution determined by laser diffraction using the assembly at all flow rates investigated. Treatment of the particle size distributions measured by laser diffraction, i.e. examining only the aerosol particles with diameter <60 μm, highlighted the fine fraction (<5 μm) and enabled the aerosolisation of different blends to be feasibly compared at a range of different flow rates. The blends containing the following excipients could be placed in the following order of increasing fine fraction: spray-dried lactose < dextrose ≪ maltose < lactose < sorbitol. At 28.3 l min −1 a significant linear correlation was found between the fine fractions measured by laser diffraction and the salbutamol fine fractions determined by inertial impaction ( R 2 = 87.4%, p = 0.02, ANOVA). Therefore, the laser diffraction technique could prove to be an important tool for particle size characterisation of dry powder aerosol formulations.