Respiratory infections are a major global health burden. The emergence and spread of drug-resistant respiratory tract pathogens, particularly Mycobacterium tuberculosis, has aggravated the current situation. High dose delivery of drugs to the lung using a dry powder inhaler (DPI) is an emerging approach to combat drug-resistant local infections. To achieve high dose delivery, highly aerosolizable powders are required. We hypothesized that co-spray-drying kanamycin, a hydrophilic hygroscopic antibiotic, with rifampicin, a hydrophobic antibiotic, would under suitable spray-drying conditions, produce particles in the inhalable size with surfaces enriched in rifampicin. We reasoned that such particles would have good aerosolization properties, would overcome problems with aerosolization of kanamycin alone, and minimise the mass of powder to be inhaled by avoiding use of non-active excipients.
Kanamycin was co-spray-dried with rifampicin using a Buchi Mini Spray-dryer. The surface composition was determined by X-ray …show more content…
XPS and ToF-SIMS showed the surface of the combination powder was enriched with rifampicin. Aerosolization was dramatically improved with the fine particle fraction (FPF) increasing from 29.5 ± 0.2% (kanamycin-only) to 78.2 ± 1.3% (kanamycin/rifampicin combination). All the spray-dried powders were noncrystalline. The combination powder was stable at 15% and 53% RH and 25 ± 2°C during one-month storage in an open Petri dish and non-toxic (max concentration tested 50 µg/mL) to human alveolar and bronchial cell-lines.
Surface enrichment of kanamycin by hydrophobic rifampicin improves aerosolization. Improved aerosolization may help to combat drug-resistant local infections by facilitating high dose delivery to deep lung. Further studies are required to distinguish the potential mechanisms for improved aerosolization and test the long-term
Kanamycin was co-spray-dried with rifampicin using a Buchi Mini Spray-dryer. The surface composition was determined by X-ray …show more content…
XPS and ToF-SIMS showed the surface of the combination powder was enriched with rifampicin. Aerosolization was dramatically improved with the fine particle fraction (FPF) increasing from 29.5 ± 0.2% (kanamycin-only) to 78.2 ± 1.3% (kanamycin/rifampicin combination). All the spray-dried powders were noncrystalline. The combination powder was stable at 15% and 53% RH and 25 ± 2°C during one-month storage in an open Petri dish and non-toxic (max concentration tested 50 µg/mL) to human alveolar and bronchial cell-lines.
Surface enrichment of kanamycin by hydrophobic rifampicin improves aerosolization. Improved aerosolization may help to combat drug-resistant local infections by facilitating high dose delivery to deep lung. Further studies are required to distinguish the potential mechanisms for improved aerosolization and test the long-term