Original article. Pharmacodynamics of dry powder formulations of salbutamol for delivery by inhalation

Abstract

Abstract Background: Salbutamol is a β2-selective adrenoceptor agonist used as a bronchodilator. Delivery by inhalation has many advantages over oral dosage for the treatment of asthma. It offers rapid onset of action with low systemic side effects. Objective: Evaluate the relationship of in vitro particle size characteristics and pharmacodynamics of formulations of inhaled salbutamol dry powder. Methods: Three formulations contained micronized salbutamol and a lactose carrier with different size ranges (40- 80, 20-40, and 10-20 μm for formulations 1, 2, and 3, respectively). Following formulation of the drug, resultant powders were characterized using scanning electron microscopy and the aerosolization performance determined using an Andersen Cascade Impactor analysis. A high-performance liquid chromatography method was used for measuring the salbutamol drug content. The in vivo pharmacodynamics of the formulations was monitored in 12 healthy and 12 asthmatic volunteers. Results: The percentage of the fine particle fractions (FPF) for formulations 1, 2, and 3 were 24.87±0.52%, 33.82±3.80%, and 41.50±2.86%, respectively. The mass median aerodynamic diameters (MMAD) were around 3 μm for all formulations. The pharmacodynamic parameters, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) and mid expiratory flow (FEF25-75), were indices for evaluation of the bioavailability of the bronchodilatory drug. All formulations improved the FEF25-75 value in asthmatics, while FVC and FEV1 were not altered. Conclusion: The formulations of salbutamol dry powder aerosols with a fine lactose carrier produced a high deposition in the lower regions of the respiratory tract. Although the FEF25-75 value in asthmatics was improved, the value did not correlate well with the FPF of the salbutamol dry powder.