A novel dry powder inhalable formulation incorporating three first-line anti-tubercular antibiotics

• Published in: European journal of pharmaceutics and biopharmaceutics 2013-02, Vol.83 (2), p.285-292
• Main Authors: Chan, John Gar Yan, Chan, Hak-Kim, Prestidge, Clive A., Denman, John A., Young, Paul M., Traini, Daniela
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosol; Aerosols - chemistry; Antibiotics; Antibiotics, Antitubercular - chemistry; Chemistry, Pharmaceutical - methods; Dry powder; Dry Powder Inhalers - methods; Excipients - chemistry; Inhalation; Mycobacterium; Particle Size; Powders - chemistry; Spray-drying; Tuberculosis
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2012.08.007

Treatment for tuberculosis (TB) using the standard oral antibiotic regimen is effective but inefficient, requiring high drug dosing and lengthy treatment times. Three concurrent first-line antibiotics recommended by the World Health Organization (WHO) guidelines are pyrazinamide, rifampicin and isoniazid. Combining these antibiotics in a novel formulation for dry powder inhalation (DPI) may facilitate rapid and efficient resolution of local and systemic infection. However, spray-dried individually, these antibiotics were found to be physically unstable. A solution of the three antibiotics, at the WHO-recommended ratio, was spray-dried. The collected powder was assessed by a series of in vitro methods to investigate aerosol performance, particle physico-chemical characteristics and dissolution profile. Particles obtained were spherical with a surface composed primarily of rifampicin, as identified by TOF-SIMS. A mass median aerodynamic diameter of 3.5±0.1μm and fine particle fraction (