Salbutamol sulfate and budesonide inhalation suspension for inhalation therapy: In vivo and in vitro evaluation.

Nebulized inhalation therapy is widely used for the treatment of acute exacerbations of asthma and COPD, in which budesonide (BUD) and salbutamol sulfate (SA) are commonly combined for synergistic anti-inflammatory and bronchodilatory effects. However, the in vitro and in vivo performance of such combination formulations remains insufficiently characterized. This study systematically evaluated the aerodynamic behavior, dissolution profiles, and pharmacokinetics/pharmacodynamics of BUD and SA inhalation suspensions. Suspensions with different volume median diameters (VMDs) were prepared by high-pressure homogenization, and their nebulization performance was assessed. Aerosol particle size distribution and pulmonary deposition were analyzed using a next-generation impactor (NGI) and a CT-based human nasal-throat airway model. The combination formulation showed a slightly higher fine particle fraction but a marginally lower total delivered dose than the single-drug formulations, with comparable droplet size and surface tension, suggesting possible aerosol interactions between the two drugs. Similar upper airway deposition was observed for both formulations, whereas pulmonary deposition was slightly reduced for the combination. In vitro dissolution studies demonstrated rapid release of SA and sustained release of BUD. In an acute lung injury model, the combination significantly improved lung histopathology and reduced TNF-α and IL-6 levels, showing superior anti-inflammatory efficacy compared with monotherapy. Pharmacokinetic analysis revealed comparable SA exposure and increased BUD Cmax and AUC in the combination formulation. Overall, the combination formulation exhibited stable aerosolization characteristics, coordinated drug release behavior, and improved pharmacodynamic performance, while increasing the systemic exposure of budesonide without significantly affecting the pharmacokinetics of salbutamol.