Enrichment of the surface of spray-dried powder particles with a hydrophobic material to improve their aerosolization

Mohammad AM Momin, Ian G Tucker, Colin Doyle, John Denman, Shyamal C Das

High dose delivery of drugs to the lung using a dry powder inhaler is an emerging approach to combat multi-drug resistant local infections. To achieve high dose delivery, high aerosolization of the powders is important. Hygroscopic drugs are a particular challenge since moisture uptake and resultant agglomeration reduces aerosolization. We hypothesize that, under appropriate conditions, a solution of hygroscopic drug and a hydrophobic compound can be spray-dried to produce particles with surfaces rich in the hydrophobic compound and this surface enrichment improves the aerosolization of these spray-dried powders.
A hygroscopic drug, kanamycin was combined with a hydrophobic drug, rifampicin (at a ratio of 3:2 w/w), and spray-dried using a Buchi Mini Spray-dryer under optimized conditions. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were used to study the surface composition. The in vitro aerosolization efficiency was investigated using a next generation impactor (NGI). The powders were also investigated for physicochemical properties.
All the spray-dried powders were within the inhalable range (1.1-5.9 μm). XPS and ToF-SIMS showed the surface of the powder was enriched with rifampicin (approximately 98% rifampicin). The fine particle fraction (FPF) significantly increased from 31.3 ± 1.8% (kanamycin-only) to 76.6 ± 3.8% (kanamycin/rifampicin combination). All the spray-dried powders were amorphous in nature.
Surface enrichment of kanamycin by hydrophobic rifampicin improves aerosolization. Improved aerosolization may be helpful to deliver high dose to the lung and combat multi-drug resistant local infections.

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