Unlocking the Microstructure of Inhalation Blends using X-ray Microscopy

Abstract

Microstructural equivalence (Q3) for dry powder inhalers (DPIs) is complex because it involves both pre- and post-aerosolization powders and can be influenced by the DPI device and the patient’s aerosolization efficiency. In this paper, we show how advanced 3D X-ray microscopy (XRM, also known as X-ray computed tomography) techniques can provide unique microstructural insights into pre-aerosolized inhalation powders. Nano-scale XRM is used to detect differences within individual lactose particles and agglomerates, including voids and intra-agglomerate size distributions. Micro-scale XRM is used to visualize and quantify lactose fines (<12 mm) within a powder bed. XRM is also used to discriminate between excipient and terbutaline sulphate particles in an inhalation blend. These advanced XRM techniques could provide valuable microstructural information to help address Q3 equivalence during bioequivalence determination in inhalation drug products.