Agglomerate strength and dispersion of salmeterol xinafoate from powder mixtures for inhalation

Handoko Adi, Ian Larson, Herbert Chiou, Paul Young, Daniela Traini, Peter Stewart

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)


Purpose: The study investigated the role of agglomeration and the effect of fine lactose size on the dispersion of salmeterol xinafoate (SX) from SX–lactose mixtures for inhalation.

Methods: Particle size distributions were characterised by Malvern Mastersizer S, Aerosizer and Spraytec, and imaging conducted by scanning electron microscopy (SEM). Inter-particulate adhesion was quantified by atomic force microscopy. Deposition of SX was measured using a twin stage impinger. SX was analysed using validated high-performance liquid chromatography method (r 2=1.0, CV=0.4–1.0%).

Results: Addition of fine lactose with a volume median diameter (VMD) of 7.9 μm to a SX–lactose carrier and carrier-free mixture resulted in significantly better dispersion (16.8% for 20% added fine lactose) than fractions with VMD of 3.0, 17.7 and 33.3 μm (less than 9.1% for 20% fine lactose). Using the carrier-free mixtures, particle sizing of the aerosol cloud using the Spraytec, coupled with the application of the Aerosizer using differing dispersion energies and SEMs of the samples, indicated that an open packed, agglomerate structure improved SX dispersion. The highest extent of SX dispersion occurred when SX and fine lactose were detached from the surface, usually in the form of loose agglomerates.

Conclusions: The outcomes of this research demonstrated how agglomerate structure influenced dispersion and the key role of fine lactose particle size in SX dispersion from mixtures for inhalation.
Original languageEnglish
Pages (from-to)2556-2565
Number of pages10
JournalPharmaceutical Research
Issue number11
Publication statusPublished - Nov 2006
Externally publishedYes


  • agglomeration
  • drug dispersion
  • dry powder inhalation
  • fine lactose
  • interactive mixture
  • salmeterol xinafoate


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