AEROSOL DELIVERY FROM AN ACTIVE EMISSION MULTI-SINGLE DOSE DRY POWDERINHALER

All commercially available dry powder inhalers depend solely on the pa tient's inspired airflow to aerosolize the drug formulation. The dose delivered is therefore subject to inter-patient variability that may b e overcome by devices actively imparting energy to the powder bed to d isperse particles. The current studies were performed to evaluate powd er filling and dose delivery from a prototype active emission multi-si ngle dose dry powder dispersion device. The device contained interchan geable cartridges (12 doses/cartridge, three cartridges with dosing ch amber diameters of 0.5, 1.0, and 1.5 mm, each 6mm in length) which wer e vacuum filled with the powder formulation. Individual doses were emi tted by compressed gas propulsion following actuator depression. Studi es were performed using bulk lactose powders (similar to 25-100 and si milar to 40-200 mu m); and sieved lactose (45-75 and 75-125 mu m), alo ne 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 par ticle size measurements and fine particle fractions were determined by inertial impaction (8-stage Andersen impactor, 60L/min). Powders fill ed 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 2 1 L/min were used to evaluate filling conditions required for optimal aerodynamic performance and dose delivery. As anticipated, the total m ass output and emitted dose delivered decreased as the dosing chamber diameter decreased. For a fixed dosing chamber diameter, the total mas s output, of drug and excipient, decreased slightly as the fill flow r ate was increased. However, the fine particle fraction and fine partic le 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 i ncrease 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 i ncrease in fine particle fraction was observed. Dose reproducibility a s indicated by standard deviations within +/-1-10%, and a mean dose re covery of 95%+/-4%, indicated acceptable performance of the device. Fu ture work will evaluate the relationship between particle size, powder flow, fill flow rate, fill density, and dose emission to optimize aer odynamic performance and dose delivery.