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Spray Drying Tailored Mannitol Carrier Particles for Dry Powder Inhalation with Differently Shaped Active Pharmaceutical Ingredients

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Process-Spray

Abstract

Dry powder inhalation as commonly used in the local therapy of asthma or chronic obstructive pulmonary disease (COPD) is a very effective route of drug delivery. The system of small cohesive drug particles attached to the surface of large carriers with particle sizes >50 μm is successfully applied to numerous marketed products. The performance of these blends is based on the particle properties of both carriers and drug particles and is usually linked to the Fine Particle Fraction (FPF), which represents the fraction of drug particles with an aerodynamic diameter of 1–5 μm, which triggers the desired effect in the lung. Mannitol, which was chosen as an alternative carrier to the market-leading α-lactose monohydrate as it is highly crystalline in contrast to lactose even after spray drying, was prepared by spray drying to generate carrier particles at a range of 50–90 μm with various morphologies. This project was first aiming at the examination of the drying kinetics of bicomponent mannitol water droplets. It could be shown that high drying temperatures cause deep indentations and increasingly rough surface structures, while low drying temperatures result in spherical particles with rough surfaces at very low drying temperatures and smoother ones when increasing temperatures. Low rotation speeds and high mass fractions increase the particle size. Further particle properties like porosity, breaking strength or flowability were related accordingly. A defined set of mannitol batches was further selected for interactive powder blends with a micronised and spray dried quality of the model drug SBS. Particle–particle interactions were then investigated by correlating carrier properties to the resulting FPF. Particle shape was found to hinder the detachment of drug particles. Rough structures dried at the lowest drying temperatures were preferred for micronised drug particles, whereas spherical drug particles were preferably detached from smoother surfaces. This effect could be related to the drug size as only the detachment of the smallest drug particles (<1 μm) tended to be affected by the roughness. Carrier size was found to decrease the FPF for larger particles, when indentations occur simultaneously. Thus, it was possible to customise the carrier properties according to the drug particle properties to finally obtain adhesive drug–carrier mixtures with optimum aerodynamic performance.

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Acknowledgements

The authors would like to thank Roquette Fréres (Lestrem, France) for providing mannitol (Pearlitol 160C) for the spray drying experiments and the group of Maike Windbergs, Saarland University, for the Raman analysis of the interactive mixtures. This project was supported by the ‘Deutsche Forschungsgesellschaft’ (DFG, German Research Foundation) in the framework of the priority program SPP 1423 ‘Process Spray’.

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Authors and Affiliations

  1. Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, Kiel, Germany

    Mathias Mönckedieck, Mats Hertel, Hartwig Steckel & Regina Scherließ

  2. Research Center Pharmaceutical Engineering, Inffeldgasse 13, Graz, Austria

    Mathias Mönckedieck, Eva Maria Littringer, Nora Anne Urbanetz & Martin Köster

  3. Department of Biochemical and Chemical Engineering, Technical University Dortmund, Emil-Figge Str. 68, Dortmund, Germany

    Jens Kamplade, Axel Mescher & Peter Walzel

  4. Interdisciplinary Center for Scientific Computing (IWR), University of Heidelberg, Heidelberg, Germany

    Srikanth Gopireddy & Eva Gutheil

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  1. Mathias Mönckedieck
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  2. Jens Kamplade
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  3. Eva Maria Littringer
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  4. Axel Mescher
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Correspondence to Regina Scherließ .

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  1. Institute of Materials Science, University of Bremen, Bremen, Germany

    Udo Fritsching

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Mönckedieck, M. et al. (2016). Spray Drying Tailored Mannitol Carrier Particles for Dry Powder Inhalation with Differently Shaped Active Pharmaceutical Ingredients. In: Fritsching, U. (eds) Process-Spray. Springer, Cham. https://doi.org/10.1007/978-3-319-32370-1_14

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