Composite carriers improve the aerosolisation efficiency of drugs for respiratory delivery

Abstract

The physico-chemical properties and aerosolisation efficiency of a dry powder inhaler (DPI) carrier system constructed from small sub-units (composite carrier) was investigated. Composite carriers were prepared by fusion of 3 μ m mannitol particles. The particles were subsequently sieved to produce a 63 – 90 μ m carrier fraction, which was compared to a sieved as-supplied crystalline material (regular carrier). The carrier particles were studied in terms of morphology (electron, optical and atomic-force microscopy), particle size (laser-diffraction), drug-carrier adhesion (colloid probe microscopy) and in vitro aerosolisation efficiency assessed using a commercially available DPI device (cascade impaction). The composite carriers morphology were similar in size and shape to the regular carrier; however, the variation in surface roughness was reduced while projected topographical surface area increased. Spatial-adhesion measurements of a model drug (salbutamol sulphate) across the surface of the carrier indicated lower variation in adhesion values and lower median adhesion forces, when compared to the regular carrier. Aerosolisation of salbutamol sulphate-composite carrier blends suggested improved drug deposition when compared to the regular carrier (fine particle fractions of 18.5 % ± 1.5 % compared to 5.6 % ± 2.9 % ). This composite approach provides improved carrier homogeneity and reduced drug-carrier adhesion resulting in improved aerosolisation efficiency.