Inhaled sildenafil nanocomposites: lung accumulation and pulmonary pharmacokinetics().

2016 
AbstractContext: Administration of sildenafil citrate (SC) is considered as a strategy in the treatment of pulmonary hypertension.Objective: This study reports production of the inhalable microparticles containing SC-loaded poly(lactide-co-glycolic acid)-nanoparticles.Methods: SC-nanoparticles were prepared by the double emulsion solvent evaporation method. Next, free SC and SC-loaded nanoparticles were spray dried in the presence of appropriate excipients (lactose, maltose and trehalose). Physicochemical properties and aerodynamic behavior of prepared powders were evaluated. In addition, drug accumulation from selected formulations in the rat lung tissue was compared with oral and IV administration.Results: Size and fine particle fraction of selected nanocomposites and free SC microparticles were 7 and 4.5 µm, and 60.2% and 68.2%, respectively. Following oral and IV administration, the drug was not detectable in the lung after 4 and 6 h, respectively, but in SC-loaded nanoparticles, the drug was detectab...
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