Adhesion and redistribution of salmeterol xinafoate particles in sugar-based mixtures for inhalation

Abstract

The aim of this study was to evaluate coarse and fine sugars as potential alternative excipients in dry powder inhalation formulations and to develop a greater understanding of the key interactions between the particulate species in these mixtures. Interactive mixtures composed of salmeterol xinafoate (SX) and different type of sugars (lactose, glucose, mannitol and sorbitol) were prepared using validated laboratory scale mixing. The sugars and SX were characterised by laser diffraction, scanning electron microscopy, atomic force microscopy and loss on drying method. Deposition of SX was measured using a twin-stage impinger and analysed using validated HPLC method ( r 2 = 1.0, CV = 0.4–1.0%). Good correlation existed between the fine particle fraction (FPF) of SX and both the adhesion force and the moisture content. The addition of 10% fine sugars to produce ternary mixtures (i.e. SX, coarse and fine sugars) generally increased dispersion, with the addition of fine glucose > fine mannitol > fine lactose > fine sorbitol. The dispersion of SX showed a reciprocal relationship with the moisture content of the sugars with glucose showing the greatest and sorbitol showing the lowest extent of SX dispersion. The study clearly demonstrated that strong SX adhesion to coarse sugars reduced the extent of dispersion and that surface detachment of the SX and fine sugar from the coarse sugar carrier was important in the dispersion process.