Comparison of in vitro and in vivo efficiencies of a novel unit-dose liquid aerosol generator and a pressurized metered dose inhaler

Gamma scintigraphic imaging was employed in 10 healthy volunteers to compare the total and regional lung deposition of aerosols generated by two delivery platforms that permitted microprocessor-controlled actuation at an optimal point during inhalation. An aqueous solution containing Tc-99m-DTPA was used to assess the deposition of aerosols delivered by inhalation from two successive unit-dosage forms (44 mu l volume) using a prototype of a novel liquid aerosol system (AERx(TM) Pulmonary Delivery SS stem). This was compared with aerosol deposition after inhalation of two 50 mu l puffs of a Tc-99m-HMPAO-labeled solution formulation from a pressurized metered dose inhaler (MDI). The in vitro size characteristics of the radiolabeled aerosols were determined by cascade impaction. For the AERs system, the predicted lung delivery efficiency based on the product of emitted dose (60.8%, coefficient of variation (CV) = 12%) and fine particle fraction (% by mass of aerosol particles < 5.7 mu m in diameter) was 53.3% (CV = 13%). For the solution MDI, the emitted dose was 62.9% (CV = 13%) and the predicted lung dose was 44.9% (CV = 15%,). The AERx system demonstrated efficient and reproducible dosing characteristics in vivo. Of the dose loaded into the device, the mean percent reaching the lungs was 53.3% (CV = 10%), with only 6.9% located in the oropharynx/stomach. In contrast, the lung deposition from the solution MDI was significantly less (21.7%) and more variable (CV = 31%), with 43.0% of the radiolabel detected in the oropharpnx/stomach. Analysis of the regional deposition of the radioaerosol indicated a homogeneous pattern of deposition after delivery from the AERx system. A predominantly central pattern of distribution occurred after MDI delivery, where the pattern of deposition was biased towards a central zone depicting the conducting airways. The AERx system, in contrast to MDIs, seems highly suited to the delivery of systemically active agents via pulmonary administration. (C) 2000 Published by Elsevier Science B.V. All rights reserved.