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Influence of Batch Cooling Crystallization on Mannitol Physical Properties and Drug Dispersion from Dry Powder Inhalers

Kaialy, Waseem, Larhrib, El Hassan, Ticehurst, Martyn and Nokhodchi, Ali (2012) Influence of Batch Cooling Crystallization on Mannitol Physical Properties and Drug Dispersion from Dry Powder Inhalers. Crystal Growth & Design, 12 (6). pp. 3006-3017. ISSN 1528-7483

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This 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 β-form (commercial mannitol) to mixtures of β- + δ-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.

Item Type: Article
Additional Information: Reprinted with permission from Cryst. Growth Des., 2012, 12 (6), pp 3006–3017 DOI: 10.1021/cg300224w Copyright 2012 American Chemical Society.
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
R Medicine > RS Pharmacy and materia medica
Schools: School of Applied Sciences
Related URLs:
Depositing User: Sara Taylor
Date Deposited: 02 Oct 2012 09:46
Last Modified: 28 Aug 2021 20:27


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