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Linking carrier morphology to the powder mechanics of adhesive mixtures for dry powder inhalers via a blend-state model
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala Univ, SDDF, Husargatan 3,Box 580, SE-75123 Uppsala, Sweden.ORCID iD: 0000-0001-5979-6670
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala Univ, SDDF, Husargatan 3,Box 580, SE-75123 Uppsala, Sweden.ORCID iD: 0000-0003-4013-9704
AstraZeneca, IMED Biotech Unit, Pharmaceut Sci, Gothenburg, Sweden.
AstraZeneca, Inhalat Prod Dev, Pharmaceut Technol & Dev, Gothenburg, Sweden.
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2019 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 561, p. 148-160Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate how the carrier morphology affects the expression of blend states in adhesive mixtures as a function of surface coverage ratio (SCR) and to identify where transitions between the different states occur. Adhesive mixtures of five lactose carriers with varying contents of lactose fines, corresponding to blends with different SCR ranging from 0 to 6, were produced by low-shear mixing. The powder mechanics of the mixtures were characterized by bulk density, compressibility and permeability. The appearance of the carriers and blends was studied by scanning electron microscopy, light microscopy and atomic force microscopy. The size and morphology of the carriers had a crucial impact on the evolution of the blend state, and affected the powder mechanical properties of the mixtures. It was found that smaller carriers with little or no surface irregularities were more sensitive to additions of fines resulting in self-agglomeration of fines at relatively low SCR values. On the contrary, carriers with irregular surface structures and larger sizes were able to reach higher SCR values before self-agglomeration of fines occurred. This could be attributed to an increased deagglomeration efficiency of irregular and larger carriers and to fines predominantly adhering to open pores.

Place, publisher, year, edition, pages
2019. Vol. 561, p. 148-160
Keywords [en]
Adhesive mixture, Ordered mixture, Inhalation powder, Powder mechanics, Blend state, Powder packing, Powder flow
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-382248DOI: 10.1016/j.ijpharm.2019.02.038ISI: 000462468700015PubMedID: 30825556OAI: oai:DiVA.org:uu-382248DiVA, id: diva2:1316035
Available from: 2019-05-15 Created: 2019-05-15 Last updated: 2019-05-15Bibliographically approved

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Rudén, JonasFrenning, GöranAn, JunxueAlderborn, Göran
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