The Preparation of a Radiolabelled Aerosol of Nedocromil Sodium for Administration by Metered-Dose Inhaler that Accurately Preserves Particle Size Distribution of the Drug

A reliable and reproducible method (method 2) for the addition of radioactive label to 2 different formulations of nedocromil sodium for delivery by metered-dose inhaler (MDI) was compared with another recently described method (method 1). The activity incorporated into the MDI expressed as a percentage of the initial radioactivity used was 28.45% for method 1 and 60.98% for method 2,. with coefficient of variation for each procedure being 38.5% and 14.26%, respectively. Both methods produced an aerosol in which the label was intimately associated with the drug. Method 1 displaced the particle size distribution of the labelled aerosol when compared to the unlabelled preparation resulting in a coarser aerosol, whereas method 2 preserved the particle size distribution. The mass median aerodynamic diameter of the fine nedocromil aerosol derived from its particle size distribution was 16.5μm (GSD 5.32). We recommend that particle size analysis of an aerosol should be assessed before and after any manipulation of that aerosol to ensure that its particle size distribution is unaffected by the manipulation.