• Journal Article

Aerosol delivery from an active emission multi-single dose dry powder inhaler


Concessio, N. M., JagerWaldau, R., & Hickey, A. (1997). Aerosol delivery from an active emission multi-single dose dry powder inhaler. Particulate Science and Technology, 15(1), 51-63. DOI: 10.1080/02726359708906709


All commercially available dry powder inhalers depend solely on the patient's inspired airflow to aerosolize the drug formulation. The dose delivered is therefore subject to inter-patient variability that may be overcome by devices actively imparting energy to the powder bed to disperse particles. The current studies were performed to evaluate powder filling and dose delivery from a prototype active emission multi-single dose dry powder dispersion device. The device contained interchangeable cartridges (12 doses/cartridge, three cartridges with dosing chamber diameters of 0.5, 1.0, and 1.5 mm, each 6mm in length) which were vacuum filled with the powder formulation. Individual doses were emitted by compressed gas propulsion following actuator depression. Studies were performed using bulk lactose powders (similar to 25-100 and similar to 40-200 mu m); and sieved lactose (45-75 and 75-125 mu m), alone and in 2% albuterol sulfate blends. Vacuum fill flow rates of 7, 14, 21, and 28 L/min were used. Filled cartridges were inserted into the device and emitted masses determined gravimetrically. Aerodynamic particle size measurements and fine particle fractions were determined by inertial impaction (8-stage Andersen impactor, 60L/min). Powders filled at a flow rate of 28L/min exhibited a high packing density and were delivered as a pellet. Consequently, lower flow rates of 7, 14, and 21 L/min were used to evaluate filling conditions required for optimal aerodynamic performance and dose delivery. As anticipated, the total mass output and emitted dose delivered decreased as the dosing chamber diameter decreased. For a fixed dosing chamber diameter, the total mass output, of drug and excipient, decreased slightly as the fill flow rate was increased. However, the fine particle fraction and fine particle mass, of drug alone, followed an opposite trend, by increasing with an increase in fill flow rate. A decrease in dosing chamber diameter resulted in an increase in air velocity (higher Re) and a subsequent increase in packing density of the filled powders at a fixed flow rate. As the dosing chamber diameters decreased (at a given fill flow rate) the total mass output and fine particle mass decreased, however, an increase in fine particle fraction was observed. Dose reproducibility as indicated by standard deviations within +/-1-10%, and a mean dose recovery of 95%+/-4%, indicated acceptable performance of the device. Future work will evaluate the relationship between particle size, powder flow, fill flow rate, fill density, and dose emission to optimize aerodynamic performance and dose delivery