Therapeutic equivalence of three metered-dose inhalers containing salbutamol (Albuterol) in protecting against methacholine-induced bronchoconstriction in children with asthma.

Many pharmaceutical companies sell salbutamol in metered-dose inhalers (MDI) for the treatment of asthma. However, the therapeutic equivalence of the more recently released generic products has not been compared with the original patented product in children. Twenty children with mild to moderate asthma, presently asymptomatic and with normal lung function, were randomly allocated to receive 200 microg of inhaled salbutamol (Albuterol) from three MDIs prepared by different manufacturers: the original Glaxo product and two generic products. The three drug formulations and placebo were given 10 min before a methacholine challenge test to determine the degree of protection provided against methacholine-induced bronchoconstriction (MIB) by each salbutamol aerosol. Tests were performed on 4 consecutive days. Doubling concentrations of methacholine were inhaled until the forced expired volume in 1 sec (FEV(1)) decreased by 20% from its baseline value. Compared to placebo, all patients increased significantly the provocation concentration that decreased FEV(1) by 20% (PC(20)) by more than one doubling concentration after inhaling each of the three salbutamol aerosols. The effectiveness was not significantly different between medications (P = 0.8). There was a small but significant difference among MDIs in aerosol particle size and total and fine-particle dose released per actuation. However, no relation was found between aerosol particle size or released dose and the protective effect. This study shows that the three tested brands of salbutamol MDI protected asthmatic children equally from MIB. When prescribing these salbutamol MDIs to prevent symptoms triggered by nonspecific stimuli in asthmatic children, the selection may be based on cost-benefit criteria.

Delivery of salbutamol pressurized metered-dose inhaler administered via small-volume spacer devices in intubated, spontaneously breathing rabbits.

Little is known about the ability of small-volume valved spacer devices to deliver a significant amount of an aerosolized drug to the lungs of babies. This study compared the in vitro delivery of salbutamol administered via Aerochamber-Infant (145 mL), Babyhaler (350 mL), and metallic NES-spacer (250 mL), as well as the in vivo delivery using an animal model. The lung deposition study of technetium-99m-labeled salbutamol was conducted in six anesthetized, intubated (3.0-mm endotracheal tube simulating oropharyngeal deposition), spontaneously breathing New Zealand White rabbits, a model for 3-kg babies. Each rabbit was studied on three separate occasions, once with each spacer device. The amount of radioactivity deposited in the spacer device, the endotracheal tube, the lungs, or the body was measured by a gamma camera and expressed as a percentage of the emitted labeled dose. The emitted dose and particle size distribution of salbutamol via the three spacer devices were measured using unit dose sampling tubes and an eight-stage Anderson cascade impactor, respectively. The results were compared by ANOVA or Student-Newman-Keuls test when indicated. In vitro, the NES-spacer and Babyhaler were equivalent for delivering particles <5.8 microm in diameter (NES-spacer = Babyhaler > Aerochamber-Infant; p < 0.05). In vivo, the lung and body deposition was low with all spacer devices (range: 0.52-5.40% of the delivered dose) but greater with the NES-spacer than with the Aerochamber-Infant or the Babyhaler (5.40 +/- 2.40%, 2.91 +/- 0.86%, 0.52 +/- 0.46%, respectively; p = 0.002). These results suggest the metal-valved spacer device may be preferable for delivering pressurized aerosols to spontaneously breathing infants.

Delivery of HFA and CFC salbutamol from spacer devices used in infancy.

The aim of the study was to compare the in vitro delivery of four salbutamol pressurized metered-dose inhalers (pMDIs) via the three spacer devices commonly used in European infants: Aerochamber-Infant, Babyhaler, and metallic NES-spacer. Emitted dose (ED) and fine particle dose (FPD, particles<5.8 microm) of each combination of spacer device and pMDI (chlorofluorocarbon-based Ventoline, Eolène, Spréor, and hydrofluoroalkane-based Airomir were measured respectively using unit dose sampling tubes (n=30 per combination) and an 8-stage cascade impactor (n=6 per group). The results were compared by analysis of variance and the Student-Newman-Keuls method. ED of Airomir was always greater than for Ventoline (P<0.05). FPD obtained with Ventoline was the lowest, with Eolène>Airomir=Spréor>Ventoline (P<0.05). Only Airomir produced a similar FPD with all three spacer devices. Chlorofluorocarbon-salbutamol pMDIs are not generics when used with spacer devices. The three spacer devices may be used interchangeably with Airomir.

Safety and efficiency of metered dose inhaler delivery of salbutamol in the intubated rabbit.

OBJECTIVE: To determine the safety and efficiency of metered dose inhaler salbutamol delivered to the intubated rabbit. DESIGN: Prospective, comparative, five-group laboratory investigation. SETTING: Animal laboratory, Department of Nuclear Medicine. SUBJECTS: A total of 30 adult, anesthetized New Zealand White rabbits. INTERVENTIONS: Three groups of rabbits underwent tracheal intubation through a tracheostomy and received 5 puffs of 99mTcO4 salbutamol delivered at the elbow connector (group 1) or via a catheter with its distal tip positioned at the midpoint (group 2) or bevel of the endotracheal tube (group 3). No intervention was provided for the rabbits in the fourth group. A fifth group underwent tracheal intubation through the mouth and received salbutamol (5 puffs) delivered at the bevel of the endotracheal tube. MEASUREMENTS: Delivery efficiency was expressed as the ratio of radioactivity emitted from lungs and trachea to the total radioactivity of the administered dose. Histopathologic injury scores were assigned to each trachea or lung specimen. MAIN RESULTS: Delivery efficiency was 30 times greater in groups 3 and 5 (full catheter) than in group 1 (elbow). The injury scores were similar in all groups. CONCLUSION: We conclude that the increased efficiency obtained by administration of metered dose inhaler salbutamol at the distal tip of endotracheal tube is not necessarily associated with increased epithelial injury.

Nicotine microaerosol inhaler.

OBJECTIVE: To measure the droplet size distribution of a nicotine pressurized metered-dose inhaler using a nicotine in ethanol solution formulation with hydrofluoroalkane as propellant. MATERIALS AND METHODS: Sizing was performed at room temperature by multistage liquid impinger and quartz crystal impactor. RESULTS: The mass median aerodynamic diameter of the nicotine aerosol produced was measured at 1.6 mm by multistage liquid impinger and 1.5 mm by quartz crystal impactor. CONCLUSIONS: The inhaler formulation used produces a microaerosol of sufficiently fine droplet size that mimics the puff-by-puff pulmonary arterial bolus nicotine delivery of tobacco smoke. The absence of combustion products such as heat, carcinogens and carbon monoxide permits safer nicotine delivery via the inhaler than is possible via smoked tobacco.