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The Influence of Relative Humidity and Storage Conditions on the Physico-chemical Properties of Inhalation Grade Fine Lactose

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Abstract

Dry powder inhalers (DPIs) are favorable devices for the delivery of dry formulations to the lungs; still, they largely fail to deliver higher doses of active pharmaceutical ingredient (API) to the lower airways. Addition of fine particles of excipient (fines) to the blend of API and carrier was shown to improve aerosolization performance. Lactose monohydrate is ubiquitous excipient used for this purpose. Lactose exists in a thermodynamically stable crystalline form; however, processes like milling, sieving, or even mixing may induce alteration of crystalline structure and introduce amorphous domains, which could further affect the physico-chemical properties of the material. Therefore, the aim of this work is a detailed characterization of two commercially available types of inhalation grade fine lactose powders (Inhalac 400 and Inhalac 500) prepared using different air-jet milling parameters, with a focus on impact of storage conditions on material properties. We found that the different milling parameters resulted in variable particle size distribution (PSD), and thus surface areas, variable initial amorphous content, cohesivity, flowability, and moisture sorption of materials. In addition, exposure of fine powders to higher humidity reduced the amorphous content present in the materials, but also affected agglomeration tendency and dispersion behavior of both powders. We believe the obtained findings to be important for the aerosolization performance of carrier-based DPIs containing fines and thus need to be duly considered during formulation development.

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Funding

This study was funded by the Austrian COMET Programme under the auspices of the Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT), the Austrian Federal Ministry of Economy, Family and Youth (BMWFJ), and the State of Styria (Styrian Funding Agency [SFG]). COMET is managed by the Austrian Research Promotion Agency (FFG).

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Author notes

  1. Milica Stankovic-Brandl and Sarah Zellnitz contributed equally to this work.

Authors and Affiliations

  1. Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010, Graz, Austria

    Milica Stankovic-Brandl, Sarah Zellnitz, Paul Wirnsberger & Amrit Paudel

  2. Institute for Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010, Graz, Austria

    Amrit Paudel

  3. MEGGLE Excipients and Technology, Megglestraße 6-12, 83512, Wasserburg, Germany

    Mirjam Kobler

Authors
  1. Milica Stankovic-Brandl
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  2. Sarah Zellnitz
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  3. Paul Wirnsberger
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  4. Mirjam Kobler
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  5. Amrit Paudel
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Contributions

Milica Stankovic-Brandl—conception and design of the work, the analysis and interpretation of the data, drafting of the manuscript. Sarah Zellnitz—interpretation of the data, critical revision of the manuscript, drafting the chapter related to charge. Paul Wirnsberger—experimental execution of part of the data, data analysis. Mirjam Kobler—revision of the manuscript. Amrit Paudel—conception and design, supervision, data interpretation, revision, and corrections.

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Correspondence to Amrit Paudel.

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Stankovic-Brandl, M., Zellnitz, S., Wirnsberger, P. et al. The Influence of Relative Humidity and Storage Conditions on the Physico-chemical Properties of Inhalation Grade Fine Lactose. AAPS PharmSciTech 23, 1 (2022). https://doi.org/10.1208/s12249-021-02159-8

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