Towards a more desirable dry powder inhaler formulation: large spray-dried mannitol microspheres outperform small microspheres.

Abstract:

PURPOSE:To investigate, for the first time, the performance of a dry powder inhaler (DPI, Aerolizer(®)) in the case of a model drug (i.e. albuterol sulphate) formulated with spray dried mannitol carrier particles with homogeneous shape and solid-state form but different sizes. METHODS:Spray dried mannitol (SDM) particles were characterized in terms of size, surface area, morphology, water content, solid-state, density and electrostatic charge by a novel approach. DPI formulations composed of SDM and albuterol sulphate (AS) were prepared and evaluated in terms of drug content homogeneity and in vitro aerosolization performance. RESULTS:All SDM particles generated similar fine particle fractions of AS. Formulations consisting of larger SDM particles demonstrated better drug content homogeneity, reduced amounts of drug loss and reduced oropharyngeal deposition. Comparing different SDM products demonstrated that SDM powders with relatively poorer flowability, wider size distributions and higher charge density generated DPI formulations with poorer drug content homogeneity and deposited higher amount of drug on the inhaler, mouthpiece adaptor and throat. DPI formulation total desirability increased linearly with the mean diameter of SDM. CONCLUSION:Particle shape and solid-state form of mannitol could dominate over carrier size, bulk density, flowability and charge in terms of determining the aerosolization behaviour of AS formulated with mannitol carrier, at least within the experimental protocols applied in the present study.

journal_name

Pharm Res

journal_title

Pharmaceutical research

authors

Kaialy W,Hussain T,Alhalaweh A,Nokhodchi A

doi

10.1007/s11095-013-1132-2

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

60-76

issue

1

eissn

0724-8741

issn

1573-904X

journal_volume

31

pub_type

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