Bedaquiline containing triple combination powder for inhalation to treat drug-resistant tuberculosis

This study aimed to develop an inhalable triple combination powder of bedaquiline, moxifloxacin and pyrazinamide and study their physicochemical properties and safety.An inhalable (aerodynamic diameter: ≤2.4 µm) triple combination powder of bedaquiline, moxifloxacin and pyrazinamide with 20% w/w of L-leucine was prepared using a Buchi Mini Spray-Dryer. Combination powder consisted of spherical and porous particles. In vitro aerosolization (fine particle fraction, FPF) determined using a next generation impactor (NGI) showed improved FPF as a combination powder (>75.0%) when compared to single drug-only formulations (<45.0%). The powder was non-toxic to A549 and Calu-3 cells up to 100 µg/mL and stable at 30 ± 2% RH and ambient room temperature during one-month storage.This is the first study reporting the development of inhalable triple combination powder of bedaquiline, moxifloxacin and pyrazinamide with high aerosolization efficiency. The improved aerosolization may help to deliver a high dose of these drugs to treat drug-resistant tuberculosis.Graphical abstract
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research