The influence of surface active L-leucine and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) in the improvement of aerosolization of pyrazinamide and moxifloxacin co-spray dried powders

摘要

Pharmacotherapy of tuberculosis is potentially more efficient when delivered by the inhaled route than by the current oral and/or parenteral routes due to the higher concentration of drug reaching the primary region of infection in the lungs. This study investigated the influence of the amino acid L-leucine alone and in combination with the phospholipid, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), on the aerosolization behaviour of the anti-TB drugs, pyrazinamide and moxifloxacin HCl. Spray dried powders of pyrazinamide (P), moxifloxacin (M) alone and in combination with 10% L-leucine (PL and ML) and 10% DPPC (PLD and MLD) were produced. The particle sizes of all powders except P were in the inhalable size range ( 5 mu m) but differ in their morphology in presence of the excipients. X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed the migration of surface active L-leucine and DPPC onto the surface of the particles during the spray drying process. The aerosolization from a dry powder inhaler, Aerolizer (R), using a Next Generation Impactor revealed fine particle fraction (FPF) values for P, PL and PLD of 18.7 +/- 3.4%, 53.0 +/- 3.2% and 74.5 +/- 5.3% respectively while FPF values for M, ML and MLD were 55.6 +/- 3.3%, 74.7 +/- 4.7% and 74.1 +/- 1.3% respectively. In conclusion, the differences in the aerosolization behaviours of the pyrazinamide and moxifloxacin spray dried powders with and without excipients was a combination of difference in the surface morphology and surface composition.