Development and characterization of high payload combination dry powders of anti-tubercular drugs for treating pulmonary tuberculosis

作者：Eedara Basanth Babu; Rangnekar Bhamini; Sinha Shubhra; Doyle Colin; Cavallaro Alex; Das Shyamal C^*

来源：European Journal of Pharmaceutical Sciences, 2018, 118: 216-226.

DOI：10.1016/j.ejps.2018.04.003

• Pyrazinamide
• Moxifloxacin
• L-leucine
• 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine
• Spray drying
• Inhalation

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 mu 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 diameter < 5 mu m and PML showed improved aerosolization with a high FPF of similar to 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 c-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 mu 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.

• 出版日期2018-6-15