In-vitro evaluation of the particle size distribution from salbutamol metered dose inhalers

Abstract EN

Objective: To evaluate the aerodynamic particle size distribution of salbutamol metered dose inhalers (lOOug per dose) using a modified Multi Stage Liquid Impinger; an impaction method used for measuring particle size distribution, and to assess the effect of the number of puffs sampled on the particle size distribution. Methods: The instrument used for the determination of the aerodynamic particle size distribution was an Astra Draco modified multistage liquid impinger (Copley Instrument, Nottingham UK) The device consists of a throat and five impaction stages.

Using a flow rate of 60 liters per minute, the effective cut - off diameters of stages 1, 2, 3 and 4 are 13.0, 6.8, 3.1 and 1.7 jxm respectively.

The fifth and final stage comprises an integral filter to capture the fraction of particles with a size less than 1.7 um.

A high-pressure liquid chromatographic method was adapted for the analysis of salbutamol. Results: The Mass Median Aerodynamic Diameter was determined for 2, 5, 10, 20, and 40 consecutive actuations using the modified Multi Stage Liquid Impinger.

The mean ± (SD) Mass Median Aerodynamic Diameter was 2.31± (0.06), 2.09 ± (0.06), 2.15 ± (0.05), 2.28 ± (0.02) and 2.10 ± (0.07)um respectively.

The geometric standard deviation values for 2, 5, 10, 20 and 40 doses were 1.40, 1.50, 1.43, 1.35 and 1.46 respectively.

The mean ± (SD) fine particle dose values for 2, 5, 10, 20 and 40 doses were 48.02 ± (2.53), 41.94± (3.05), 47.12 ± (2.89), 54.61± (1.43) and 52.7 ± (2.09) respectively. Conclusion: The results in this study showed differences between aerodynamic particle size distributions when a different number of doses were used. The Mass Median Aerodynamic Diameter increased as the number of doses increased from five to twenty doses, while the results showed violation at two and forty doses, this could be due to a number of factors such as: Inadequate extraction of the drug from the different stages of the Multi Stage Liquid Impinger, or problems in the HPLC analysis. Key words: Salbutamol; Metered Dose Inhalers; Particle Size Distribution; Mass Median Aerodynamic Diameter, Multi Stage Liquid Impinger.