Role of Agglomeration in the Dispersion of Salmeterol Xinafoate from Mixtures for Inhalation with Differing Drug to Fine Lactose Ratios

Abstract

The purpose of this study was to characterise the role of agglomeration on salmeterol xinafoate (SX) dispersion from mixtures for inhalation by varying the SX concentration and the proportion of fine lactose (FL). SX concentrations and SX:FL ratios ranged from 1.0% to 5.0% (w/w) and from 1:0 to 1:8, respectively. The in vitro deposition of SX was measured using a twin stage impinger (TSI). The aerosol was characterized by particulate capture in the TSI stages and subsequent imaging by scanning electron microscopy and by real-time particle sizing. The presence of coarse lactose reduced SX dispersion compared with SX alone, and the dispersion was independent of SX concentration. SX dispersion in binary mixtures of SX and FL was independent of SX:FL ratio and was similar to that of carrier-based mixtures with high particulate loads. Increased concentrations of SX and proportions of FL in carrier-based mixtures resulted in increased SX dispersion. Agglomerate formation coincided with increased dispersion. The study demonstrated that agglomeration is one of the important factors in SX dispersion from carrier-based mixtures at high particulate loads.