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Agglomerate Strength and Dispersion of Salmeterol Xinafoate from Powder Mixtures for Inhalation

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Abstract

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.

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Acknowledgments

Handoko Adi was supported by a Monash University Postgraduate Scholarship. All lactose samples were donated by Foremost Farms, USA; Meggle, Germany; and Lactose New Zealand, NZ. Salmeterol xinafoate was donated by Glaxo Australia.

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Authors and Affiliations

  1. Department of Pharmaceutics, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia

    Handoko Adi, Ian Larson & Peter Stewart

  2. Advanced Drug Delivery Group, Faculty of Pharmacy (A15), University of Sydney, Sydney, NSW, 2006, Australia

    Herbert Chiou, Paul Young & Daniela Traini

Authors
  1. Handoko Adi
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  2. Ian Larson
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  3. Herbert Chiou
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  4. Paul Young
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  5. Daniela Traini
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  6. Peter Stewart
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Correspondence to Peter Stewart.

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Adi, H., Larson, I., Chiou, H. et al. Agglomerate Strength and Dispersion of Salmeterol Xinafoate from Powder Mixtures for Inhalation. Pharm Res 23, 2556–2565 (2006). https://doi.org/10.1007/s11095-006-9082-6

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  • DOI: https://doi.org/10.1007/s11095-006-9082-6

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