Engineered mannitol ternary additives improve dispersion of lactose-salbutamol sulphate dry powder inhalations.
Abstract
The aim of this study was to evaluate the influence of novel engineered fine mannitol particles (4.7%, w/w) on the performance of lactose-salbutamol sulphate dry powder inhaler (DPI) formulations to obtain promising aerosolisation properties. The results showed that the more elongated the fine mannitol particles, the weaker the drug-carrier adhesion, the better the drug content homogeneity, the higher the amount of drug expected to be delivered to the lower airways and the higher the total DPI formulation desirability. Linear relationships were established showing that mannitol particles with a more elongated shape generated powders with broader size distributions and that were less uniform in shape. The weaker the drug-carrier adhesion, the higher the fine particle fraction of the drug is upon aerosolisation. It is believed that more elongated fine mannitol particles reduce the number of drug-carrier and drug-drug physical contact points and increase the ability of the drug particles to travel into the lower airways. Additionally, a lower drug-carrier contact area, lower drug-carrier press-on forces and easier drug-carrier detachment are suggested in the case of formulations containing more elongated fine mannitol particles. Ternary 'drug-coarse carrier-elongated fine ternary component' DPI formulations were more favourable than both 'drug-coarse carrier' and 'drug-elongated coarse carrier' binary formulations. This study provides a comprehensive approach for formulators to overcome the undesirable properties of dry powder inhalers, as both improved aerosolisation performance and reasonable flow characteristics were obtained using only a small amount of elongated engineered fine mannitol particles.Citation
Engineered mannitol ternary additives improve dispersion of lactose-salbutamol sulphate dry powder inhalations. 2013, 15 (3):728-43 AAPS JPublisher
SpringerJournal
The AAPS journalPubMed ID
23591748Type
Journal articleLanguage
enISSN
1550-7416ae974a485f413a2113503eed53cd6c53
10.1208/s12248-013-9476-4
Scopus Count
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