Influence of batch cooling crystallization on mannitol physical properties and drug dispersion from dry powder inhalers
journal contribution
posted on 2023-06-08, 19:20 authored by Waseem Kaialy, Hassan Larhrib, Martyn Ticehurst, Ali NokhodchiThis study provides, for the first time, an evaluation of the physicochemical properties of batch cooling crystallized mannitol particles combined with how these properties correlated with the inhalation performance from a dry powder inhaler (Aerolizer). The results showed that the type of polymorph changed from ß-form (commercial mannitol) to mixtures of ß- + d-mannitol (cooling crystallized mannitol crystals). In comparison to mannitol particles, crystallized at a higher supersaturation degree, a lower degree of supersaturation favored the formation of mannitol crystals with a more regular and elongated habit, smoother surface, higher specific surface area, higher fine particle content, higher bulk density, and higher tap density. Cooling crystallized mannitol particles demonstrated considerably lower salbutamol sulfate-mannitol adhesion in comparison to commercial mannitol, with a linear reduction as surface roughness decreased and fines content increased. Also, mannitol crystals with smoother surfaces demonstrated a reduction in salbutamol sulfate content uniformity (expressed as %CV) within salbutamol sulfate-mannitol formulations. Despite the different physical properties, all mannitol products showed similar flow properties and similar emission of salbutamol sulfate upon inhalation. However, mannitol crystals grown from lower supersaturation (reduced roughness and increased fines) generated a finer aerodynamic size distribution and consequently deposited higher amounts of salbutamol sulfate on lower stages of the impactor. Regression analysis indicated linear relationships showing higher fine particle fraction of salbutamol sulfate in the case of mannitol particles having a more elongated shape, higher fines content, higher specific surface area, higher bulk density, and higher tap density. In conclusion, a cooling crystallization technique could be controlled to produce mannitol particles with controlled physical properties that could be used to influence aerosolization performance of a dry powder inhaler product. © 2012 American Chemical Society.
History
Publication status
- Published
Journal
Crystal Growth & DesignISSN
1528-7483Publisher
American Chemical SocietyExternal DOI
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6Volume
12Page range
3006-3017Department affiliated with
- Chemistry Publications
Full text available
- No
Peer reviewed?
- Yes
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2014-12-18Usage metrics
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