Agglomerate properties and dispersibility changes of salmeterol xinafoate from powders for inhalation after storage at high relative humidity

Purpose: This study investigated changes in agglomeration and the mechanism of dispersibility decrease of salmeterol xinafoate (SX) from SX–lactose mixtures for inhalation after storage at 75% RH for 3 months. Methods: The dispersibility, PSD and in situ PSD of aerosol plumes of SX alone and SX–coarse lactose (CL) mixtures containing 0, 5, 10 and 20% micronized lactose (ML) before and after storage were determined by a Next Generation Impactor (NGI), a Mastersizer 2000 and a Spraytec, respectively. Results: The PSD of ML increased after storage at 75% RH, but dispersibility of SX using the stored ML increased. After storage, the %SX of the mixture containing 20% ML (M20F) significantly increased (P < 0.05) in the throat and mouthpiece, preseparator and stage 1 of NGI, while it significantly decreased in the remaining stages (P < 0.05). In situ analysis of aerosol plumes of M20F supported this result with an increased presence of particles of 4–25 μm and a decreased respirable particle distribution of <4 μm after storage. Conclusions: The decreased dispersibility of M20F after storage was due to the formation of less dispersible agglomerates, probably occurring through enhanced capillary interaction and/or solid bridging of ML, entrapping and preventing the release of SX particles.