The purpose of this study was to prepare spray dried bosentan microparticles for dry powder inhaler and to characterize its physicochemical and aerodynamic properties. The microparticles were prepared from ethanol/water solutions containing bosentan using spray dryer. Three types of formulations (SD60, SD80, and SD100) depending on the various ethanol concentrations (60%, 80%, and 100%, respectively) were used. Bosentan microparticle formulations were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, differential scanning calorimetry, Fourier-transform infrared spectroscopy, dissolution test, and in vitro aerodynamic performance using Andersen cascade impactor^™ (ACI) system. In addition, particle image velocimetry (PIV) system was used for directly confirming the actual movement of the aerosolized particles. Bosentan microparticles resulted in formulations with various shapes, surface morphology, and particle size distributions. SD100 was a smooth surface with spherical morphology, SD80 was a rough surfaced with spherical morphology and SD60 was a rough surfaced with corrugated morphology. SD100, SD80, and SD60 showed significantly high drug release up to 1 h compared with raw bosentan. The aerodynamic size of SD80 and SD60 was 1.27 µm and SD100 was 6.95 µm. The microparticles with smaller particle size and a rough surface aerosolized better (%FPF: 63.07 ± 2.39 and 68.27 ± 8.99 for SD60 and SD80, respectively) than larger particle size and smooth surface microparticle (%FPF: 22.64 ± 11.50 for SD100).

This study aimed to prepare mucus-penetrating inhalable microparticles for dry powder inhalers and to evaluate their applicability in an asthma-induced rat model. Microparticles were prepared from water solutions containing tiotropium bromide, L-leucine, and sodium glycocholate (NaGc) as permeation enhancers using the spray drying method. Four formulations (SDL1, SDL2, SDL3, and SDL4) were used, depending on the various NaGc concentrations. Tiotropium microparticles were characterized by standard methods. Additionally, an asthma-induced rat model was used to confirm the effects of the formulations on lung function. Tiotropium microparticles with NaGc resulted in formulations with a more corrugated morphology and smaller particle size distribution than those without NaGc. SDL 1 had a rough surface with irregular morphology, and SDL 2, 3, and 4 had a corrugated morphology. All SDL formulations had an aerodynamic size of <3 µm. The microparticles with a corrugated morphology aerosolized better than SDL1 microparticles. The apparent permeability coefficient (P_app) values of SDL3 and SDL4 were significantly higher than those for raw tiotropium. In an in vivo study using an asthma-induced rat model, the specific airway resistance (S_raw), airway wall thickness, and mean alveolus size recovered to those of the negative control group in the SDL4 formulation.