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

Waseem Kaialy, Hassan Larhrib, Martyn Ticehurst, Ali Nokhodchi

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

LanguageEnglish
Pages3006-3017
Number of pages12
JournalCrystal Growth and Design
Volume12
Issue number6
Early online date10 May 2012
DOIs
Publication statusPublished - 6 Jun 2012

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mannitol
Mannitol
Crystallization
Powders
drugs
Physical properties
physical properties
crystallization
Cooling
cooling
Supersaturation
Pharmaceutical Preparations
Albuterol
Crystals
Sulfates
sulfates
Specific surface area
fines
Surface roughness
supersaturation

Cite this

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title = "Influence of Batch Cooling Crystallization on Mannitol Physical Properties and Drug Dispersion from Dry Powder Inhalers",
abstract = "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.",
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Influence of Batch Cooling Crystallization on Mannitol Physical Properties and Drug Dispersion from Dry Powder Inhalers. / Kaialy, Waseem; Larhrib, Hassan; Ticehurst, Martyn; Nokhodchi, Ali.

In: Crystal Growth and Design, Vol. 12, No. 6, 06.06.2012, p. 3006-3017.

Research output: Contribution to journalArticle

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AU - Ticehurst, Martyn

AU - Nokhodchi, Ali

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