The role of fines in the modification of the fluidization and dispersion mechanism within dry powder inhaler formulations

J Shur, H Harris, Matthew Jones, J S Kaerger, Robert Price

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

Abstract

Purpose. To investigate the role of in situ generated fine excipient particles on the fluidization and aerosolization properties of dry powder inhaler (DPI) formulations. Materials and Methods. Carrier based DPI formulations were prepared under low and high shear blending. Powder rheometery was utilized to measure bulk powder properties in a consolidated and aerated state. Powder fluidization and aerosolization characteristics were related to bulk powder properties using high speed imaging and inertial impaction measurements. Results. High shear blending of formulations resulted in the in situ generation of excipient fines, which corresponded to an increase in aerosolization efficiency. The generation of fines were shown to increase the tensile strength and free volume of the carrier, which resulted in a characteristic change in the fluidization properties, as observed by high speed imaging. The increase in minimum fluidization velocity and aerodynamic drag forces required to aerate the powder may provide the source of energy for the increase in fine particle re-suspension. Conclusions. The in situ generation of excipient fines affect bulk powder properties of DPI formulations, which directly affects fluidization and aerosolization behaviour of DPI formulations. The study suggests an alternative mode of action by which fines increase DPI formulation performance.
Original languageEnglish
Pages (from-to)1631-1640
Number of pages10
JournalPharmaceutical Research
Volume25
Issue number7
Early online date1 Feb 2008
DOIs
Publication statusPublished - 1 Jul 2008

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