Inhalation therapy with a nebulizer is widely used in chronic respiratory disease. Mixing inhalation solutions/suspensions for simultaneous inhalation is more convenient and might simplify the administration procedure. However, there are no data available to address the in vitro aerosol characteristics and physico-chemical compatibility of Combivent^® (containing Salbutamol and Ipratropium bromide) with other inhalation solutions/suspensions. In order to investigate the in vitro aerosol characteristics and physico-chemical compatibility of Combivent^® with Budesonide, Beclomethasone, and N-acetylcysteine, the appearance, pH, osmotic pressure, chemical stability, mass median aerodynamic diameter (MMAD), fine particles fraction (FPF), particle size corresponding to X50 (particle size, which accounts for 50% of the total cumulative percentage of volume of all particles), delivery rate, and total delivery of the mixed inhalation solution/suspension were tested. There was no change in the appearance such as a change in color or precipitation formation at room temperature. The pH, osmolality, and chemicals of the mixtures were stable for 24 h after mixing. There were no significant differences between Combivent^®, Budesonide, Beclomethasone, N-acetylcysteine, and the mixtures in MMAD, FPF, X50, the delivery rate, and the total delivery. This indicates that the mixtures were physically and chemically compatible. The mixing did not influence the particle size, distribution, or delivery compatibility of the mixtures.

Sepsis is a severe life-threatening condition caused by a dysregulated host response to infection. So far, there are no pharmacotherapies to stop sepsis. Salbutamol, a commonly used β ₂ -adrenoreceptor agonist, has found to be potential in regulating immune response dysfunction and exert anti-inflammatory effect. However, salbutamol exists two isomers. R-isomer exhibits the therapeutic effect and clinical benefit, while S-isomer proves to be detrimental rather than benign. So, in this study, we investigated the preventive and therapeutic effect of R-salbutamol (R-sal), S-salbutamol (S-sal) or racemic mixture in a mouse model of lipopolysaccharide (LPS)-induced sepsis. Dexamethasone (Dex) was set as comparison. The results showed that R-sal markedly improved seven-day survival rate of septic mice both administered before or after LPS. Whereas Dex showed toxic and accelerated the death of septic mice when given before LPS injection. Lung histological examination and lung function assay revealed that LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa and congestion, and decreased minute volume in septic mice. R-sal pretreatment efficiently inhibited these changes, accompanying by markedly reduced lung MPO level, serum cytokines levels and lactate release and significantly restored the lymphocytes and suppressed the percentage of monocytes. Racemic mixture exhibited diminished effects while S-sal showed enhanced cytokines release. In addition, R-sal pretreatment showed a better improvement in prognostic pulmonary function at day4 in survived mice than that of Rac-sal. Collectively, our results indicate the potential benefit of R-sal for sepsis and sepsis-induced lung injury.