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

PurposeThis 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.MethodsThe 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.ResultsThe 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.ConclusionsThe 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.