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The influence of physical properties and morphology of crystallised lactose on delivery of salbutamol sulphate from dry powder inhalers.
Kaialy, Waseem Martin, Gary P Larhrib, Hassan Ticehurst, Martyn D Kolosionek, Ewa Nokhodchi, Ali
Kaialy, Waseem
Martin, Gary P
Larhrib, Hassan
Ticehurst, Martyn D
Kolosionek, Ewa
Nokhodchi, Ali
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2011-09-10
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Abstract
The aim of this work was to investigate the mechanistic evaluation of physicochemical properties of new engineered lactose on aerosolisation performance of salbutamol sulphate (SS) delivered from dry powder inhaler (DPI). Different crystallised lactose particles were obtained from binary mixtures of butanol:acetone. The sieved fractions (63-90 μm) of crystallised lactose were characterised in terms of size, shape, flowability, true density and aerosolisation performance (using multiple twin stage impinger (MSLI), Aerolizer(®) inhaler device, and salbutamol sulphate as a model drug). Compared to commercial lactose, crystallised lactose particles were less elongated, covered with fine lactose particles, and had a rougher surface morphology. The crystallised lactose powders had a considerably lower bulk and tap density and poorer flow when compared to commercial lactose. Engineered carrier with better flow showed improved drug content homogeneity, reduced amounts of drug "deposited" on the inhaler device and throat, and a smaller drug aerodynamic diameter upon inhalation. Aerodynamic diameter of salbutamol sulphate increased as lactose aerodynamic diameter decreased (linear, R(2)=0.9191) and/or as fine particle lactose content increased (linear, R(2)=0.8653). Improved drug aerosolisation performance in the case of crystallised lactose particles was attributed to lower drug-carrier adhesion forces due to a rougher surface and higher fine particle content. In conclusion, this work proved that using binary combinations of solvents in crystallisation medium is vital in modification of the physicochemical and micromeritic properties of carriers to achieve a desirable aerosolisation performance from DPI formulations. Among all lactose samples, lactose particles crystallised from pure butanol generated the highest overall DPI formulations desirability.
Citation
Kaialy, W. et al. (2012) The influence of physical properties and morphology of crystallised lactose on delivery of salbutamol sulphate from dry powder inhalers, Colloids and Surfaces B: Biointerfaces, 89, pp. 29-39
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Research Unit
PubMed ID
21962946
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Journal article
Language
en
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ISSN
1873-4367