title: Gamma scintigraphic evaluation of a miniaturized AERx pulmonary delivery system for aerosol delivery to anesthetized animals using a positive pressure ventilation system.
abstract: The purpose of this study was to characterize performance of a miniaturized AERx((R)) Pulmonary Delivery System designed for aerosol administration to large animal models. The miniaturized AERx System was developed through a systematic scaling down of the AERx System used for humans to allow for operation in certain animal models with lower inspiratory flow rates and inhaled volumes than those used for humans. We used gamma scintigraphy to characterize the in vivo particle deposition achieved with the miniaturized AERx System in two dogs. The dogs were 3-4 years old, and weighed 10.4 kg and 13.6 kg. Acepromazine was used as pre-anesthetic medication. Anesthesia was induced with 5% isoflurane. The trachea was intubated using an endotracheal tube (internal diameter 8.5 mm), and the dogs were ventilated using positive pressure during the exposure using the LRRI puff generator. An inhalation of aerosol was initiated by activation of the puff generator though the computer-controlled interface. Each dog inhaled approximately 0.8 L per puff, of which the aerosol volume comprised approximately 0.25 L, at a target flow rate of 15 L/min. The dogs were exposed to 10 AERx Strips in 10 puffs. The mass median aerodynamic diameter of the aerosolized formulation was approximately 1.25 microm with a fine particle fraction <3.5 microm of 0.976. The scintigraphic images showed uniform bilateral lung deposition following aerosol delivery with the AERx System. Total lung deposition for the two dogs was 10.7% and 18% of the loaded dose from the AERx Strip. The corresponding peripheral lung: inner lung (P/I) ratios were 0.83 and 0.75, suggestive of deposition in the deep lung. Only 0.1% to 0.2% of the loaded dose was exhaled. These results show the miniature AERx System can efficiently deliver aerosols to the deep lung of dogs. The miniaturized AERx System would be a valuable tool for conducting proof-of-concept studies as well as safety and tolerability analysis of inhaled drug candidates in large animal models.
authors.affiliation: Aradigm Corporation, Hayward, CA 94545, USA. deshpanded@aradigm.com
authors.forename: Deepa S
authors.initials: DS
authors.lastname: Deshpande
authors.forename: James D
authors.initials: JD
authors.lastname: Blanchard
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schuster
authors.forename: Dallas
authors.initials: D
authors.lastname: Fairbanks
authors.forename: Charles
authors.initials: C
authors.lastname: Hobbs
authors.forename: Robert
authors.initials: R
authors.lastname: Beihn
authors.forename: Charles
authors.initials: C
authors.lastname: Densmore
authors.forename: Stephen
authors.initials: S
authors.lastname: Farr
authors.forename: Igor
authors.initials: I
authors.lastname: Gonda
mesh_terms: D000280:Administration, Inhalation; D000336:Aerosols; D000768:Anesthesia, General; D000818:Animals; D004285:Dogs; D016503:Drug Delivery Systems; D008168:Lung / Q000000981:diagnostic imaging*; D008904:Miniaturization; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011175:Positive-Pressure Respiration / Q000295:instrumentation*; D011877:Radionuclide Imaging; D013670:Sodium Pertechnetate Tc 99m
chemical_list: D000336:Aerosols; D013670:Sodium Pertechnetate Tc 99m