Manipulation of spray-drying conditions to develop dry powder particles with surfaces enriched in hydrophobic material to achieve high aerosolization of a hygroscopic drug
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Date
2018
Authors
Momin, M.A.M.
Tucker, I.G.
Doyle, C.S.
Denman, J.A.
Das, S.C.
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International Journal of Pharmaceutics, 2018; 543(1-2):318-327
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This study aimed to develop dry powder particles with surfaces enriched in hydrophobic material by manipulation of spray-drying conditions and to investigate the effect of hydrophobic surface enrichment on aerosolization of hygroscopic drug. The composite dry powder formulations of kanamycin (hygroscopic drug) and rifampicin ( hydrophobic drug) were produced by systematically (2 3 full factorial design) varying the drug ratio, co-solvent composition and inlet temperature using Buchi B-290 Mini Spray-Dryer. All the composite powder particles were inhalable in size (3.1-3.9 µm), wrinkled, flake-shaped and amorphous. X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry showed that hydrophobic surface enrichment was significantly affected by co-solvent composition. Complete hydrophobic surface enrichment was achieved in one formulation (F7). The aerosolization efficiency by next generation impactor (NGI) showed that the composite formulations had higher fine particle fraction (FPF: > 48.0%) than kanamycin-only formulation (FPF: 27.6%). Increase in hydrophobic surface enrichment (from 80.8 to 100%) decreased the powder density and increased FPF (from 48.0 to 77.2%). This is the first systematic study reporting the manipulation of spray-drying conditions for hydrophobic surface enrichment in composite dry powder particles and its effect on aerosolization. The high aerosolization efficiency of the combination formulations may be useful to deliver high doses of these drugs to treat lung infections.
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Copyright 2018 Elsevier
Access Condition Notes: Accepted manuscript available after 1 April 2019