The role of fines in the modification of the fluidization and dispersion mechanism within dry powder inhaler formulations.
OBJECTIVE
To investigate the role of in situ generated fine excipient particles on the fluidization and aerosolization properties of dry powder inhaler (DPI) formulations.


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.
Shur
Jagdeep
J
Pharmaceutical Surface Science Group, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA27AY, UK.
Harris
Haggis
H
Jones
Matthew D
MD
Kaerger
J Sebastian
JS
Price
Robert
R
D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D007091:Image Processing, Computer-Assisted; D007785:Lactose / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders / Q000737:chemistry*; D013499:Surface Properties
D001993:Bronchodilator Agents; D005079:Excipients; D011208:Powders; D019819:Budesonide; D007785:Lactose