Co-deposition of salmeterol and fluticasone propionate by a combination inhaler

The combination of the long-acting beta2-agonist, salmeterol xinafoate (salmeterol) and inhaled corticosteroid, fluticasone propionate (FP) (Seretide/Advair) has shown enhanced efficacy compared with concurrent administration of the two drugs from individual inhalers at the same dose. A possible explanation for this increased effect is a higher degree of co-deposition of the two drugs from the combination (Seretide) inhaler compared with the component drugs administered separately. Raman laser spectroscopy, a technique capable of identifying individual drug particles, has been used with novel statistical methodology that we have developed, to determine whether there is any co-association between drug particles and whether this occurs in the Seretide formulation rather than by chance. Samples from a combined Seretide metered dose inhaler (MDI, 25/50 mcg) and salmeterol (25 mcg) with FP (50 mcg) from separate MDI's taken from Plate 4 of an Anderson Cascade Impactor were analysed. Using a statistical test based on the bootstrap technique, it was found that the co-deposition of FP and salmeterol particles from the combination MDI was significantly greater than from the separate inhalers group (p < 0.001). A higher degree of co-deposition on the same cells of the airways may possibly account for the increased efficacy observed in patients prescribed Seretide MDI.