Development and characterization of high payload combination dry powders of anti-tubercular drugs for treating pulmonary tuberculosis
Date
2018
Authors
Eedara, B.B.
Rangnekar, B.
Sinha, S.
Doyle, C.
Cavallaro, A.
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European Journal of Pharmaceutical Sciences, 2018; 118:216-226
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Abstract
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 (P SD ) and moxifloxacin (M SD ) and combination powders of the two drugs without (PM) and with 10% L-leucine (PML) and 10% DPPC (PMLD) were produced by spray drying. P SD contained > 10 μm 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 diameter < 5 μm and PML showed improved aerosolization with a high FPF of ~70%. However, PMLD showed a significantly reduced FPF (p > 0.05) 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 μg/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.
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Copyright 2018 Elsevier