Preparation and in vitro characterization of clofazimine-loaded albumin nanocomposite microparticles for inhalation therapy

The aim of this study was to develop and characterize inhalable clofazimine-loaded albumin nanocomposite microparticles for the treatment of tuberculosis. Clofazimine-loaded albumin nanoparticles (CLZ-HSA-NPs) were prepared by a desolvation method. The effect of pH of the albumin solution, the amount of crosslinking agent and of the active pharmaceutical ingredient to albumin ratio on the CLZ-HSA-NPs is discussed. The albumin nanocomposites were prepared by spray drying method using mannitol alone or in combination with 10 % or 20 % leucine as matrix. After formulation optimization of the albumin nanocomposites, 20 % albumin nanoparticle/70 % mannitol/10 % leucine (20 %NP/70 %M/10 %L) nanocomposite microparticles were selected as the optimized formulation. The nanocomposite comprising this optimized inhalation formulation formed spherical particles with a fine particle fraction (FPF) of 25.5 ± 7.7 %. Homogeneous and stable CLZ-HSA-NPs were obtained after re-dispersion in water. Compared with bulk clofazimine, clofazimine-loaded nanocomposites exhibited rapid drug dissolution (74.9 ± 2.7 %, after 15 min). The amount of cellular uptake and the antibacterial effect of clofazimine in the nanocomposite microparticles were comparable to that of clofazimine solution. The albumin nanocomposite particles prepared in this study could be a promising inhalation formulation for clofazimine, a highly hydrophobic drug.