Microstructural insight into inhalation powder blends through correlative multi-scale X-ray computed tomography

Abstract

Dry powder inhalers (DPI) are important for topical drug delivery to the lungs, but characterising the pre-aerosolised powder microstructure is a key initial step in understanding the post-aerosolised blend performance. In this work, we characterise the pre-aerosolised 3D microstructure of an inhalation blend using correlative multi-scale X-ray Computed Tomography (XCT), identifying lactose and drug-rich phases at multiple length scales on the same sample. The drug-rich phase distribution across the sample is shown to be homogeneous on a bulk scale but heterogeneous on a particulate scale, with individual clusters containing different amounts of drug-rich phase, and different parts of a carrier particle coated with different amounts of drug-rich phase. Simple scalings of the drug-rich phase thickness with carrier particle size are used to derive the drug-proportion to carrier particle size relationship. This work opens new doors to micro-structural assessment of inhalation powders that could be invaluable for bioequivalence assessment of dry powder inhalers.

Keywords: Correlative tomography; Inhalation; Microstructural equivalence; Microstructure; Powder characterisation; X-ray computed tomography.