The enhanced aerosol performance of salbutamol from dry powders containing engineered mannitol as excipient.

Published on Jun 15, 2010in International Journal of Pharmaceutics5.875
· DOI :10.1016/J.IJPHARM.2010.03.057
Waseem Kaialy23
Estimated H-index: 23
(Medway School of Pharmacy),
Gary P. Martin61
Estimated H-index: 61
('KCL': King's College London)
+ 2 AuthorsAli Nokhodchi63
Estimated H-index: 63
(Tabriz University of Medical Sciences)
The aim of the present study was to investigate the effect of crystallising mannitol from different binary mixtures of acetone/water on the resultant physical properties and to determine the effects of any changes on in vitro aerosolisation performance, when the different mannitol crystals were used as a carrier in dry powder inhaler formulations containing salbutamol sulphate. Mannitol particles were crystallised under controlled conditions by dissolving the sugar in water and precipitating the sugar using binary mixtures of acetone/water in different percentages as anti-solvent media. For comparison purposes the physical properties and deposition behaviour of commercially available mannitol were also studied. SEM showed that all crystallised mannitol particles were more elongated than the commercial mannitol. Solid state studies revealed that commercial mannitol and mannitol crystallised using acetone in the presence of 10-25% v/v water as anti-solvent was β-polymorphic form whereas mannitol crystallised in the presence of a small amount of water (0-7.5%) was the α-form. All the crystallised mannitol samples showed poor flowability. Nevertheless, the powdered crystallised mannitol and commercial samples were blended with salbutamol in the ratio 67.5:1. The aerosolisation performance of the formulations containing the engineered mannitol (evaluated using Multi Stage Liquid Impinger) was considerably better than that of the commercial mannitol formulation (the fine particle fraction was increased from 15.42% to 33.07-43.99%, for the formulations containing crystallised mannitol). Generally, carriers having a high tapped density and high fraction of fine carrier particles produced a high FPF. The improvement in the DPI performance could be attributed to the presence of elongated carrier particles with smooth surfaces since these are believed to have less adhesive forces between carrier and the drug resulting in easier detachment of the drug during the inhalation. © 2010 Elsevier B.V.
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