An aerosol formulation of R-salbutamol sulfate for pulmonary inhalation

Abstract

An aerosol formulation containing 7.5 mg of R-salbutamol sulfate was developed. The aerosol was nebulized with an air-jet nebulizer, and further assessed according to the new European Medicines Agency (EMA) guidelines. A breath simulator was used for studies of delivery rate and total amount of the active ingredient at volume of 3 mL. A next generation impactor (NGI) with a cooler was used for analysis of the particle size and in vitro lung deposition rate of the active ingredient at 5 °C. The anti-asthmatic efficacy of the aerosol formulation was assessed in guinea pigs with asthma evoked by intravenous injection of histamine compared with racemic salbutamol. Our results show that this aerosol formulation of R-salbutamol sulfate met all the requirements of the new EMA guidelines for nebulizer. The efficacy of a half-dose of R-salbutamol equaled that of a normal dose of racemic salbutamol.

Keywords: Asthma; Dose uniformity; Guinea pigs; NGI; Nebulizer; Particle size; R-salbutamol.

Graphical abstract

Figure 1

Drug deposition rate for four aerosol solutions in different stages. Data are expressed as mean±SD, n=3.

Figure 2

Effect of inhaling R-salbutamol and racemic salbutamol on R_aw (A) and C_dyn (B). The animals were divided into two groups (each group has eight guinea pigs, 4 males and 4 females): I, inhaling saline (control) following R-salbutamol (0.2 mg/mL, 30 s) and II, inhaling saline (control) following racemic salbutamol (0.4 mg/mL, 30 s). The data are expressed as mean±SE, n=8. **P<0.01 vs. control group.