TY - JOUR
T1 - Microstructural insight into inhalation powder blends through correlative multi-scale X-ray Computed Tomography
AU - Gajjar, P.
AU - Styliari, I.d.
AU - Legh-Land, V.
AU - Bale, H.
AU - Tordoff, B.
AU - Withers, P. J.
AU - Murnane, D.
N1 - Funding Information:
The authors of this paper were all part of the INFORM2020 consortium, which was funded through EPSRC grant EP/N025075/1. We are grateful to consortium partner DFE Pharma and to Meggle for providing the raw materials. We further acknowledge Kindeva Drug Delivery, Astra Zeneca, Glaxo Smith Kline, Malvern Panalytical and Carl Zeiss Microscopy for their membership and support of the INFORM2020 consortium. PG is grateful for support from colleagues at Seda Pharmaceutical Development Services in completing this work. PG also acknowledges support from EP/M010619/1. PJW acknowledges funding from an ERC advanced grant Correl-CT (No. 695638). Beamtime for this study was kindly provided by the Henry Moseley X-ray Imaging Facility (HMXIF), which was established through EPSRC grants EP/F007906/1, EP/I02249X/1 and EP/F028431/1, and is now part of the National Research Facility for Laboratory-based X-ray CT (NXCT), funded through EPSRC grant EP/T02593X/1. HMXIF is also a part of the Henry Royce Institute for Advanced Materials, established through EPSRC grants EP/R00661X/1, EP/P025498/1 and EP/P025021/1.
Funding Information:
The authors of this paper were all part of the INFORM2020 consortium, which was funded through EPSRC grant EP/N025075/1. We are grateful to consortium partner DFE Pharma and to Meggle for providing the raw materials. We further acknowledge Kindeva Drug Delivery, Astra Zeneca, Glaxo Smith Kline, Malvern Panalytical and Carl Zeiss Microscopy for their membership and support of the INFORM2020 consortium. PG is grateful for support from colleagues at Seda Pharmaceutical Development Services in completing this work. PG also acknowledges support from EP/M010619/1. PJW acknowledges funding from an ERC advanced grant Correl-CT (No. 695638). Beamtime for this study was kindly provided by the Henry Moseley X-ray Imaging Facility (HMXIF), which was established through EPSRC grants EP/F007906/1, EP/I02249X/1 and EP/F028431/1, and is now part of the National Research Facility for Laboratory-based X-ray CT (NXCT), funded through EPSRC grant EP/T02593X/1. HMXIF is also a part of the Henry Royce Institute for Advanced Materials, established through EPSRC grants EP/R00661X/1, EP/P025498/1 and EP/P025021/1.
Publisher Copyright:
© 2023 The Authors
PY - 2023/10/1
Y1 - 2023/10/1
N2 - 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.
AB - 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.
KW - X-ray Computed Tomography
KW - Microstructural equivalence
KW - Powder characterisation
KW - Inhalation
KW - Correlative Tomography
KW - Microstructure
KW - Correlative tomography
KW - X-ray computed tomography
UR - http://www.scopus.com/inward/record.url?scp=85171473287&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/4ab3b880-09a8-3d87-ac05-e9cee8da559d/
U2 - 10.1016/j.ejpb.2023.08.016
DO - 10.1016/j.ejpb.2023.08.016
M3 - Article
SN - 0939-6411
VL - 191
SP - 265
EP - 275
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -