Development and characterization of high payload combination dry powders of anti‐tubercular drugs for treating pulmonary tuberculosis
Abstract
&NA; This study aimed to develop a high payload dry powder inhalation formulation containing a combination of the first line anti‐tubercular drug, pyrazinamide, and the second line drug, moxifloxacin HCl. Individual powders of pyrazinamide (PSD) and moxifloxacin (MSD) and combination powders of the two drugs without (PM) and with 10% l‐leucine (PML) and 10% DPPC (PMLD) were produced by spray drying. PSD contained >10&mgr;m crystalline particles and showed poor aerosolization behaviour with a fine particle fraction (FPF) of 18.7±3.4%. PM produced spherical hollow particles with aerodynamic diameter0.05) compared to PML. Solid state studies and surface elemental analysis by X‐ray photoelectron spectroscopy and time‐of‐flight secondary ion mass spectrometry confirmed the surface coating of particles contained amorphous moxifloxacin and both l‐leucine and DPPC over crystalline pyrazinamide. Furthermore, pyrazinamide, moxifloxacin, PML and PMLD were found to display low toxicity to both A549 and Calu‐3 cell lines even at a concentration of 100&mgr;g/mL. In conclusion, a combination powder formulation of PML has the potential to deliver a high drug dose to the site of infection resulting in efficient treatment. Graphical abstract: Symbol. No Caption available.
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