Effect of particle morphology on emitted dose of fatty acid-treated disodium cromoglycate powder aerosols

Abstract

These studies assess the quantity and morphology of the emitted aerosolized dose of irregularly shaped disodium cromoglycate particles in the fine particle fraction using in vitro methods. Disodium cromoglycate was treated with a homologous series of saturated fatty acids, between C8 and C18, in a range of concentrations. The products of these treatments were powders with a variety of particle size, shape, and aggregation characteristics. Samples of these powders were loaded in gelatin capsules, generated as aerosols from a Rotahaler and collected in a two-stage liquid impinger or eight-stage inertial impactor. Particles were examined directly by scanning electron microscopy and subsequently the images were analyzed to define morphology. The aerodynamic fine-particle fraction determined by the two-stage impinger increased approximately twofold with lauric acid treatment (0.0317 g/g, 6.7%) and threefold with stearic acid treatment (0.58 g/g; 9.7%) compared with disodium cromoglycate alone (0 g/g, 3.56%). The lauric acid formulation appeared to alter deposition primarily by changing particle morphology. Stearic acid altered particle shape to some extent and the increase in the fine-particle fraction appeared to be attributable to improved particle dispersion properties. The uncontrolled presence of irregular-shaped particles can introduce dosing errors due to effects on dispersion and aerodynamic behavior. Conversely, controlled particle morphology and size may be employed to optimize the dose delivered to the lungs particularly if particle-particle and particle-surface interactions can be minimized