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Towards a More Desirable Dry Powder Inhaler Formulation: Large Spray-Dried Mannitol Microspheres Outperform Small Microspheres

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ABSTRACT

Purpose

To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer®) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid–state form but different sizes.

Methods

Spray dried mannitol (SDM) particles were characterized in terms of size, surface area, morphology, water content, solid–state, density and electrostatic charge by a novel approach. DPI formulations composed of SDM and albuterol sulphate (AS) were prepared and evaluated in terms of drug content homogeneity and in vitro aerosolization performance.

Results

All SDM particles generated similar fine particle fractions of AS. Formulations consisting of larger SDM particles demonstrated better drug content homogeneity, reduced amounts of drug loss and reduced oropharyngeal deposition. Comparing different SDM products demonstrated that SDM powders with relatively poorer flowability, wider size distributions and higher charge density generated DPI formulations with poorer drug content homogeneity and deposited higher amount of drug on the inhaler, mouthpiece adaptor and throat. DPI formulation total desirability increased linearly with the mean diameter of SDM.

Conclusion

Particle shape and solid–state form of mannitol could dominate over carrier size, bulk density, flowability and charge in terms of determining the aerosolization behaviour of AS formulated with mannitol carrier, at least within the experimental protocols applied in the present study.

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors thank Dr. I.J. Slipper (University of Greenwich) for help provided with SEM analyses. Waseem Kaialy and Ali Nokhodchi thank Dr. D. Tong (University of Greenwich) for access to powder charge analyses, as well as Dr. M. Maniruzzaman and Dr. D. Douroumis (University of Greenwich) for access to BET surface area analyses. Merck KGaA (Germany) is acknowledged for providing delta mannitol (Parteck® Delta M).

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Authors and Affiliations

  1. Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB, Kent, UK

    Waseem Kaialy & Ali Nokhodchi

  2. Pharmaceutics and Pharmaceutical Technology Department School of Pharmacy,, University of Damascus, Damascus, Syria

    Waseem Kaialy

  3. The Wolfson Centre for Bulk Solids Handling Technology Medway School of Engineering, University of Greenwich, Chatham Maritime, Kent, UK

    Tariq Hussain

  4. ALS Scandinavia AB, Aurorum 10, 977 75, Luleå, Sweden

    Amjad Alhalaweh

  5. Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Ali Nokhodchi

Authors
  1. Waseem Kaialy
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  2. Tariq Hussain
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  3. Amjad Alhalaweh
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  4. Ali Nokhodchi
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Correspondence to Waseem Kaialy.

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Kaialy, W., Hussain, T., Alhalaweh, A. et al. Towards a More Desirable Dry Powder Inhaler Formulation: Large Spray-Dried Mannitol Microspheres Outperform Small Microspheres. Pharm Res 31, 60–76 (2014). https://doi.org/10.1007/s11095-013-1132-2

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  • DOI: https://doi.org/10.1007/s11095-013-1132-2

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