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Dry powder inhalers: physicochemical and aerosolization properties of several size-fractions of a promising alterative carrier, freeze-dried mannitol

journal contribution
posted on 2023-06-09, 00:04 authored by Waseem Kaialy, Ali Nokhodchi
The purpose of this work was to evaluate the physicochemical and inhalation characteristics of different size fractions of a promising carrier, i.e., freeze-dried mannitol (FDM). FDM was prepared and sieved into four size fractions. FDMs were then characterized in terms of micromeritic, solid-state and bulk properties. Dry powder inhaler (DPI) formulations were prepared using salbutamol sulphate (SS) and then evaluated in terms of drug content homogeneity and in vitro aerosolization performance. The results showed that the crystalline state of mannitol was maintained following freeze-drying for all size fractions of FDM. All FDM particles showed elongated morphology and contained mixtures of a-, ß- and d-mannitol. In comparison to small FDM particles, FDMs with larger particle sizes demonstrated narrower size distributions, higher bulk and tap densities, lower porosities and better flowability. Regardless of particle size, all FDMs generated a significantly higher (2.2–2.9-fold increase) fine particle fraction (FPF, 37.5 ± 0.9%–48.6 ± 2.8%) of SS in comparison to commercial mannitol. The FPFs of SS were related to the shape descriptors of FDM particles; however, FPFs did not prove quantitative apparent relationships with either particle size or powder bulk descriptors. Large FDM particles were more favourable than smaller particles because they produced DPI formulations with better flowability, better drug content homogeneity, lower amounts of the drug depositing on the throat and contained lower fine-particle-mannitol. Optimized stable DPI formulations with superior physicochemical and pharmaceutical properties can be achieved using larger particles of freeze-dried mannitol (FDM).

History

Publication status

  • Published

Journal

European Journal of Pharmaceutical Sciences

ISSN

0928-0987

Publisher

Elsevier

Volume

68

Page range

56-67

Department affiliated with

  • Chemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2016-01-18

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