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Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate
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Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate
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Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate
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Journal Article
Preparation and Evaluation of Mucus-Penetrating Inhalable Microparticles of Tiotropium Bromide Containing Sodium Glycocholate
2022
Overview
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 (Papp) 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 (Sraw), airway wall thickness, and mean alveolus size recovered to those of the negative control group in the SDL4 formulation.
Publisher
MDPI AG,MDPI
Subject
