Microstructural insight into inhalation powder blends through correlative multi-scale X-ray computed tomography
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.
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Materials
Inhalation grade alpha lactose monohydrate (true density 1.54 g cm-3), namely Lactohale 100 was donated by DFE Pharma (Germany), whilst micronised Fluticasone Proprionate (micFP, true density 1.37 g cm-3) was purchased from Coral Pharma (India).
Parmesh Gajjar, Ioanna Danai Styliari, Victoria Legh-Land, Hrishikesh Bale, Benjamin Tordoff, Philip J. Withers, Darragh Murnane, Microstructural insight into inhalation powder blends through correlative multi-scale X-ray computed tomography, European Journal of Pharmaceutics and Biopharmaceutics, Volume 191, 2023, Pages 265-275, ISSN 0939-6411, https://doi.org/10.1016/j.ejpb.2023.08.016.
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